Pathway modulator, pharmaceutical composition having same, use thereof, and therapeutic method using same

Abstract

A pathway modulator, a pharmaceutical composition having same, use thereof, and a therapeutic method using same. The pathway modulator (comprising one or more of a dopamine β-hydroxylase inhibitor, a receptor agonist and a receptor antagonist) can inhibit development of autoimmune diseases by immunoregulation, thereby providing potential therapeutic drugs for the treatment of autoimmune diseases.

Description

Pathway regulators, pharmaceutical compositions containing the same, their uses, and treatment methods using the same This disclosure claims the priority of a Chinese patent application (application number 2021101034359) filed on January 26, 2021. Technical Field This disclosure relates to pathway regulators, pharmaceutical compositions containing the same, their uses, and treatment methods using the same. Background Art Dopamine β-hydroxylase (hereinafter referred to as DBH), also known as dopamine β-monooxygenase, is an enzyme (EC 1.14.17.1) encoded by the DBH gene in the human body. DBH catalyzes the oxidation of dopamine by oxygen to norepinephrine and epinephrine as follows: DBH is a copper-containing oxygenase of approximately 290 kDa, which consists of four identical subunits, and its activity requires ascorbic acid as a cofactor [1]. DBH is the only enzyme involved in the synthesis of small molecule membrane-bound neurotransmitters, which makes norepinephrine the only neurotransmitter synthesized within vesicles. Norepinephrine is expressed in noradrenergic nerve endings in the central and peripheral nervous systems and chromaffin cells in the adrenal medulla. DBH mainly contributes to the biosynthesis of trace amines and catecholamines, including epinephrine (or adrenaline), norepinephrine (or noradrenaline), and dopamine. In addition, it is also involved in the metabolism of exogenous biogenic substances related to these substances. For example, human DBH catalyzes the β-hydroxylation of amphetamine and p-hydroxyamphetamine to produce norephedrine and p-hydroxynorephedrine [2-4]. DBH is considered to be related to disorders of thinking and decision-making and drug addiction, such as alcoholism [5] and smoking [6], attention deficit hyperactivity disorder [7], schizophrenia [8], and Alzheimer's disease [9]. And DBH deficiency is called dopamine β-hydroxylase deficiency. In the late 20th and early 21st centuries, Nepicastat

[0010] , Etamicastat

[0011] , Zamicastat

[0012] These highly selective DBH inhibitors have also been further studied for their potential uses in pulmonary arterial hypertension, congestive heart failure, cocaine dependence, or post-traumatic stress disorder (PTSD), etc. Nepicastat may be used for the treatment of congestive heart failure and shows good tolerance in patients.

[0013] . Further clinical research data indicate that nepicastat has no effect in the treatment of heart failure but has safety. Nepicastat and its analogs (such as etamicastat, imicastat) have potential uses in the treatment of hypertension. Clinical trials evaluating nepicastat for the treatment of PTSD and cocaine dependence have been completed. The study found that when nepicastat is co-administered with cocaine, nepicastat is safe and can inhibit the positive effects of cocaine. This result suggests that nepicastat can be used as a drug therapy for the treatment of cocaine dependence.

[0014] . Compared with nepicastat, etamicastat and imicastat have lower levels of penetration across the blood-brain barrier, can reduce the norepinephrine level in tissues innervated by the peripheral sympathetic nervous system, and have no effect on the brain tissue of spontaneously hypertensive rats.

[0015] . This result suggests that DBH inhibitors such as etamicastat and imicastat can reduce adverse reactions or complications of the central nervous system when treating peripheral-related diseases. In a Phase II clinical study, it was observed that etamicastat (200 mg) dose-dependently reduced systolic and diastolic blood pressure after 10 days of treatment and showed good tolerance and safety.

[0016] . Imicastat (1200 mg) also showed good safety when administered continuously for 10 days (NCT02151994). Currently, a clinical trial of imicastat for the efficacy of pulmonary arterial hypertension is underway (NCT04316143). The role of DBH in immunomodulation was first reported in a study in 1998. The study found that under pathogen-free conditions, the white blood cell count, T and B cell development, and in vitro functions of dbh- / - mice were normal, but dbh- / - mice were more susceptible to infection by pathogens (such as Listeria monocytogenes or Mycobacterium tuberculosis); at the same time, the animals showed severe thymic involution and impaired T cell function, including the production of Th1 cytokines. These results suggest that physiological normal development does not require the production of catecholamines, but catecholamines play an important role in the immunomodulation of infection.

[0017] . As a part of the autonomic nervous system, DBH directly and indirectly penetrates the entire brain source, tissues, blood vessels, and peripheral blood through noradrenergic fibers. In addition to noradrenergic fibers, the expression and localization of its protein also have certain tissue specificity. For example, DBH is expressed at a certain level in chromaffin cells of the adrenal medulla, noradrenergic cells of the locus coeruleus, liver tissue, and intestinal tissue, and the expression of DBH in the adrenal medulla is the highest. A certain study found that high expression of DBH in tissues or high levels of DBH secretion in peripheral blood may be associated with some neurological or endocrine diseases.

[0018] For example, high levels of DBH in peripheral blood may be associated with Alzheimer's disease, bipolar disorder, Huntington's disease, hypothyroidism, and PTSD. Although the level of DBH in peripheral blood may be associated with neurological diseases, DBH inhibitors have not shown good efficacy for Alzheimer's disease and PTSD in clinical trials (see the database of CLINICALTRIALS). Similarly, another study found that in patients with autoimmune enteritis, the expression of DBH was upregulated in inflamed tissues, but the study did not clarify the inevitable connection between the two.

[0019] . According to the Autoimmune Association, there are more than 100 types of autoimmune diseases. Clinically, for the treatment of autoimmune diseases, the main approach is to use hormones and / or immunosuppressive drugs in a non-targeted manner to control symptoms, which at the same time brings great and irreversible adverse reactions and damages to patients. Therefore, finding a safe therapeutic agent for treating autoimmune diseases is a technical problem that urgently needs to be solved in this field. Summary of the Invention The technical problems to be solved by the present disclosure include providing a pathway regulator, a pharmaceutical composition containing the same, its uses, and a treatment method using the same. The inventors unexpectedly found that pathway regulators in the prior art, including one or more of dopamine β-hydroxylase inhibitors (abbreviated as DBH inhibitors), receptor agonists, and receptor antagonists, can inhibit the occurrence and development of autoimmune diseases through immunomodulation (for example, specifically reflected in the improvement of weight loss, the improvement of DAI scores, and the normalization of colon density), and thus can provide potential therapeutic drugs for the treatment of autoimmune diseases. The present disclosure solves the above technical problems through the following technical solutions: A first aspect of the present disclosure relates to the use of a pathway regulator in the preparation of a drug for treating autoimmune diseases; wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist. In the above use, the pathway regulator is preferably a DBH inhibitor. In the above-mentioned use, the DBH inhibitor can be a DBH inhibitor that has been disclosed in the prior art or a subsequent one. By way of example, it can be one or more of nepicastat, etamicastat, imicastat, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nepicastat, etamicastat, imicastat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nepicastat, etamicastat and imicastat. Treating autoimmune diseases with one or more of nepicastat, etamicastat and imicastat will not cause great and irreversible adverse reactions and damages to patients brought by non-targeted drugs of hormones and / or immunosuppressants, and it is a safe therapeutic agent capable of treating autoimmune diseases. In the above-mentioned use, the DBH inhibitor is preferably selected from nepicastat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nepicastat. Treating autoimmune diseases with nepicastat can significantly reduce the weight loss of patients and significantly reduce the colon density of patients. In the above-mentioned use, by way of example: The pathway regulator is nepicastat or its pharmaceutically acceptable salt, and the unit dose is: 10 - 100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20 - 50 mg / kg; or, The pathway regulator is etamicastat or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is imicastat or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg. In the context, the unit dose can be an integer or a fraction. It should be understood that, for example, "10 to 100" is a concise writing method, and although not every point value within this range is given, it is regarded as having been clearly disclosed in the text. The above technical solution is used for treating autoimmune diseases, and can significantly reduce the weight loss of patients and significantly reduce the colon density of patients. In the above uses, the autoimmune disease may be one or more of the autoimmune diseases disclosed in the prior art, and may be selected, for example, from achalasia, Addison's disease, Adult Still's disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-GBM / Anti-TBM nephritis, Antiphospholipid syndrome, Autoimmune angioedema, Autoimmune dysautonomia, Autoimmune encephalomyelitis, Autoimmune hepatitis, Autoimmune inner ear disease (abbreviated as AIED), Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune orchitis, Autoimmune pancreatitis, Autoimmune retinopathy, Autoimmune urticaria, Axonal&neuronal neuropathy (abbreviated as AMAN), Baló disease, Behcet's disease, Benign mucosal pemphigoid, Bullous pemphigoid, Castleman disease (abbreviated as CD), Celiac disease, Chagas disease, Chronic inflammatory demyelinating polyneuropathy,Abbreviations: CIDP (Chronic Inflammatory Demyelinating Polyneuropathy), CRMO (Chronic Recurrent Multifocal Osteomyelitis), EGPA (Eosinophilic Granulomatosis with Polyangiitis), Cicatricial pemphigoid, Cogan’s syndrome, Cold agglutinin disease, Congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn’s disease, Dermatitis herpetiformis, Dermatomyositis, Devic’s disease (neuromyelitis optica), Discoid lupus, Dressler’s syndrome, Endometriosis, Eosinophilic esophagitis,Abbreviations: EoE), Eosinophilic fasciitis, Erythema nodosum, Essential mixed cryoglobulinemia, Evans syndrome, Fibromyalgia, Fibrosing alveolitis, Giant cell arteritis, Giant cell myocarditis, Glomerulonephritis, Goodpasture’s syndrome, Granulomatosis with Polyangiitis, Graves’disease, Guillain-Barre syndrome, Hashimoto’s thyroiditis, Hemolytic anemia, Henoch-Schonlein purpura (abbreviation HSP), Herpes gestationis or pemphigoid gestationis (abbreviation PG), Hidradenitis Suppurativa (abbreviation HS), Hypogammalglobulinemia, IgA Nephropathy, IgG4-related sclerosing disease, Immune thrombocytopenic purpura (abbreviation ITP), Inclusion body myositis (abbreviation IBM), Interstitial cystitis (abbreviation IC), Juvenile arthritis, Juvenile diabetes Type 1, Juvenile myositis,Abbreviations JM), Kawasaki disease, Lambert-Eaton syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, Linear IgA disease (abbreviation LAD), Lupus, Lyme disease chronic, Meniere’s disease, Microscopic polyangiitis (abbreviation MPA), Mixed connective tissue disease (abbreviation MCTD), Mooren’s ulcer, Mucha-Habermann disease (acute pityriasis lichenoides varioliformis acuta), Multifocal Motor Neuropathy (abbreviation MMN or MMNCB), Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neonatal Lupus, Neutropenia, Ocular cicatricial pemphigoid, Optic neuritis, Palindromic rheumatism (abbreviation PR), PANDAS, Paraneoplastic cerebellar degeneration (abbreviation PCD), Paroxysmal nocturnal hemoglobinuria,Abbreviations: PNH), Parry Romberg syndrome, Pars planitis, Parsonage-Turner syndrome, Pemphigus, Peripheral neuropathy, Perivenous encephalomyelitis, Pernicious anemia (abbreviation: PA), POEMS syndrome, Polyarteritis nodosa, Polyglandular syndromes type I, Polyglandular syndromes type II, Polyglandular syndromes type III, Polymyalgia rheumatica, Polymyositis, Postmyocardial infarction syndrome, Postpericardiotomy syndrome, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progesterone dermatitis, Psoriasis, Psoriatic arthritis, Pure red cell aplasia (abbreviation: PRCA), Pyoderma gangrenosum, Raynaud’s phenomenon, Reactive Arthritis, Reflex sympathetic dystrophy, Relapsing polychondritis, Restless legs syndrome,Abbreviations: RLS), Retroperitoneal fibrosis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma, Sjogren's syndrome, syndrome), Sperm & testicular autoimmunity, Stiff person syndrome (abbreviation SPS), Subacute bacterial endocarditis (abbreviation SBE), Susac's syndrome, Sympathetic ophthalmia (abbreviation SO), Takayasu's arteritis, Temporal arteritis / Giant cell arteritis, Thrombocytopenic purpura (abbreviation TTP), Thyroid eye disease (abbreviation TED), Tolosa - Hunt syndrome (abbreviation THS), Transverse myelitis, Type 1 diabetes, Ulcerative colitis (abbreviation UC), Undifferentiated connective tissue disease (abbreviation UCTD), Uveitis, Vasculitis, Vitiligo, and Vogt - Koyanagi - Harada Disease; preferably autoimmune colitis, neuromyelitis optica, rheumatoid arthritis, scleroderma, psoriasis, or uveitis. The second aspect of the present disclosure relates to a pathway regulator for treating autoimmune diseases; wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist. Among the above - mentioned pathway regulators, the pathway regulator is preferably a DBH inhibitor. Among the above-mentioned pathway regulators, the DBH inhibitor can be a DBH inhibitor disclosed in the prior art. For example, it can be one or more of nialamide, etomidate, imidate, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nialamide, etomidate, imidate, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nialamide, etomidate and imidate. Among the above-mentioned pathway regulators, the DBH inhibitor is preferably selected from nialamide, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nialamide. Among the above-mentioned pathway regulators, as an example: The pathway regulator is nialamide or its pharmaceutically acceptable salt, and the unit dose is: 10 - 100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20 - 50 mg / kg; or, The pathway regulator is etomidate or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is imidate or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. Among the above pathway regulators, the definition of the autoimmune disease is as defined above. The third aspect of the present disclosure relates to a method for treating an autoimmune disease, which comprises the step of administering to a subject a therapeutically effective amount of a pathway regulator; wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist. In the above treatment method, the pathway regulator is preferably a DBH inhibitor. In the above treatment method, the DBH inhibitor can be a DBH inhibitor disclosed in the prior art, for example, it can be one or more of nialamide, etomidate, emetine, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts, and its prodrugs. The DBH inhibitor is preferably selected from nialamide, etomidate, emetine, its pharmaceutically acceptable salts, and its prodrugs. The DBH inhibitor is more preferably selected from nialamide, etomidate, and emetine. In the above treatment method, the DBH inhibitor is preferably selected from nialamide, its pharmaceutically acceptable salts, and its prodrugs. The DBH inhibitor is more preferably nialamide. In the above treatment method, the DBH inhibitor can be administered in combination with one or more selected from chemotherapeutic agents, targeted therapeutic agents, immunotherapeutic agents, and anti-inflammatory agents. In the above treatment method, by way of example: The pathway regulator is nialamide or a pharmaceutically acceptable salt thereof, and the unit dose is: 10 - 100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or a range between any two of the foregoing values; preferably 20 - 50 mg / kg; or, The pathway regulator is etomidate or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is emixustat or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg. In the above treatment method, the autoimmune disease is defined as defined above. The fourth aspect of the present disclosure relates to a pharmaceutical composition for treating an autoimmune disease, which comprises: - a pathway regulator, and - a pharmaceutically acceptable carrier; Wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist. In the above pharmaceutical composition, the pathway regulator is preferably a DBH inhibitor. In the above pharmaceutical composition, the DBH inhibitor can be a DBH inhibitor disclosed in the prior art, for example, it can be one or more of nipisat, etamiselast, emixustat, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nipisat, etamiselast, emixustat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nipisat, etamiselast and emixustat. In the above pharmaceutical composition, the DBH inhibitor is preferably selected from nipisat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nipisat. In the above-mentioned pharmaceutical composition, as an example: The pathway regulator is nepicastat or a pharmaceutically acceptable salt thereof, and the unit dose is: 10 - 100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or a range between any two of the foregoing values; preferably 20 - 50 mg / kg; or, The pathway regulator is etamicastat or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is imicastat or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. In the above-mentioned pharmaceutical composition, the definition of the autoimmune disease is as defined above. The fifth aspect of the present disclosure relates to the use of a pathway regulator in the preparation of a drug; the drug is used for one or more of the following uses: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, increasing the proportion of CD8+ T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, reducing the secretion of pro-inflammatory factors by CD8+ T cells, inhibiting the activation of B cells and inhibiting the activation of NK cells; reducing the content of lymphocytes, neutrophils and monocytes in peripheral blood; reducing inflammatory cell infiltration in the dermis and capillary hyperplasia under the dermis; improving skin fibrosis; reducing the incidence of uveitis; improving skin inflammation; improving fecal formability score, improving CW / CL, improving CW / BW, improving CW / CL / BW, inhibiting the increase in colonic ulcer area, improving colonic inflammatory cell infiltration score, improving tissue damage score; improving disease activity score, improving blood in stool or occult blood. Among them, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist and a receptor antagonist. In the above uses, the pathway regulator is preferably a DBH inhibitor. In the above uses, the DBH inhibitor can be a DBH inhibitor already disclosed in the prior art, for example, it can be one or more of nialamide, etomidate, emetine, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nialamide, etomidate, emetine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nialamide, etomidate and emetine. In the above uses, the DBH inhibitor is preferably selected from nialamide, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nialamide. In the above uses, as an example: The pathway regulator is nialamide or its pharmaceutically acceptable salt, and the unit dose is: 10-100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20-50 mg / kg; or, The pathway regulator is etomidate or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is emistat or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or a range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. In the above uses, the drug is preferably used for one or more of the following uses: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, inhibiting the activation of B cells, and inhibiting the activation of NK cells. In the above uses, the pro-inflammatory factors of the CD4+ T cells are preferably one or more of IL-17A, IFN-γ, and TNF-α. In the above uses, the pro-inflammatory factors of the CD8+ T cells are preferably IL-17A and / or TNF-α. In the above uses, the regulatory T cells are preferably CD25+FOXP3+ Treg cells. In the above uses, the B cells are preferably B220+ cells, more preferably CD69+B220+ B cells. In the above uses, the NK cells are preferably NK1.1+ cells, more preferably NK1.1+CD107a+ NK cells. The sixth aspect of the present disclosure relates to a pathway regulator for use in one or more of the following: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, increasing the proportion of CD8+ T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, reducing the secretion of pro-inflammatory factors by CD8+ T cells, inhibiting the activation of B cells and inhibiting the activation of NK cells; reducing the content of lymphocytes, neutrophils and monocytes in peripheral blood; reducing inflammatory cell infiltration in the dermis and capillary proliferation under the dermis; improving skin fibrosis; reducing the incidence of uveitis; improving skin inflammation; improving fecal formability score, improving CW / CL, improving CW / BW, improving CW / CL / BW, inhibiting the increase in colonic ulcer area, improving colonic inflammatory cell infiltration score, improving tissue damage score; improving disease activity score, improving blood in stool or occult blood. Among them, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist and a receptor antagonist. Among the above-mentioned pathway regulators, the pathway regulator is preferably a DBH inhibitor. Among the above-mentioned pathway regulators, the DBH inhibitor can be a DBH inhibitor already disclosed in the prior art, such as nipicastat, etamicastat, emicastat, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, one or more of its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nipicastat, etamicastat, emicastat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nipicastat, etamicastat and emicastat. Among the above-mentioned pathway regulators, the DBH inhibitor is preferably selected from nipicastat, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nipicastat. Among the above-mentioned pathway regulators, as an example: The pathway regulator is nipicastat or its pharmaceutically acceptable salt, and the unit dose is: 10-100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20-50 mg / kg; or, The pathway regulator is etamicastat or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is emistat or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. Among the above pathway regulators, the drug is preferably used for one or more of the following uses: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, inhibiting the activation of B cells, and inhibiting the activation of NK cells. Among the above pathway regulators, the pro-inflammatory factors of the CD4+ T cells are preferably one or more of IL-17A, IFN-γ, and TNF-α. Among the above pathway regulators, the pro-inflammatory factors of the CD8+ T cells are preferably IL-17A and / or TNF-α. Among the above pathway regulators, the regulatory T cells are preferably CD25+FOXP3+ Treg cells. Among the above pathway regulators, the B cells are preferably B220+ cells, more preferably CD69+B220+ B cells. Among the above pathway regulators, the NK cells are preferably NK1.1+ cells, more preferably NK1.1+CD107a+ NK cells. The seventh aspect of the present disclosure relates to a method for regulating the function of immune cells in vivo or in vitro, which includes the following steps: contacting an effective amount of a pathway regulator with immune cells in vivo or in vitro, wherein the immune cells are from a subject; wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist; The regulation of immune cell function refers to one or more functions selected from the following: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, increasing the proportion of CD8+ T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, reducing the secretion of pro-inflammatory factors by CD8+ T cells, inhibiting the activation of B cells, and inhibiting the activation of NK cells. In the above method, the pathway regulator is preferably a DBH inhibitor. In the above method, the DBH inhibitor can be a DBH inhibitor disclosed in the prior art, such as, for example, nialamide, etomidate, imidate, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, one or more of its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nialamide, etomidate, imidate, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nialamide, etomidate and imidate. In the above method, the DBH inhibitor is preferably selected from nialamide, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nialamide. In the above method, as an example: The pathway regulator is nialamide or its pharmaceutically acceptable salt, and the unit dose is: 10-100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20-50 mg / kg; or, The pathway regulator is etomidate or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is imidate or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. In the above method, the DBH inhibitor can be administered in combination with one or more selected from chemotherapeutic agents, targeted therapeutic agents, immunotherapeutic agents, and anti-inflammatory agents. In the above method, the drug is preferably used for one or more of the following uses: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, inhibiting the activation of B cells, and inhibiting the activation of NK cells. In the above method, the pro-inflammatory factors of the CD4+ T cells are preferably one or more of IL-17A, IFN-γ, and TNF-α. In the above method, the pro-inflammatory factors of the CD8+ T cells are preferably IL-17A and / or TNF-α. In the above method, the regulatory T cells are preferably CD25+FOXP3+ Treg cells. In the above method, the B cells are preferably B220+ cells, more preferably CD69+B220+B cells. In the above method, the NK cells are preferably NK1.1+ cells, more preferably NK1.1+CD107a+ NK cells. The eighth aspect of the present disclosure relates to a pharmaceutical composition comprising a pathway regulator and a pharmaceutically acceptable carrier; wherein, the pathway regulator is one or more of a DBH inhibitor, a receptor agonist, and a receptor antagonist; The pharmaceutical composition has one or more functions selected from the following: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, increasing the proportion of CD8+ T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, reducing the secretion of pro-inflammatory factors by CD8+ T cells, inhibiting the activation of B cells and inhibiting the activation of NK cells; reducing the content of lymphocytes, neutrophils and monocytes in peripheral blood; reducing inflammatory cell infiltration in the dermis and capillary hyperplasia under the dermis; improving skin fibrosis; reducing the incidence of uveitis; improving skin inflammation; improving fecal formability score, improving CW / CL, improving CW / BW, improving CW / CL / BW, inhibiting the increase in colonic ulcer area, improving colonic inflammatory cell infiltration score, improving tissue damage score; improving disease activity score, improving blood in stool or occult blood. In the above pharmaceutical composition, the pathway regulator is preferably a DBH inhibitor. In the above pharmaceutical composition, the DBH inhibitor can be a DBH inhibitor disclosed in the prior art, for example, it can be one or more of nialamide, etomidate, imidate, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is preferably selected from nialamide, etomidate, imidate, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably selected from nialamide, etomidate and imidate. In the above pharmaceutical composition, the DBH inhibitor is preferably selected from nialamide, its pharmaceutically acceptable salts and its prodrugs. The DBH inhibitor is more preferably nialamide. In the above pharmaceutical composition, as an example: The pathway regulator is nialamide or its pharmaceutically acceptable salt, and the unit dose is: 10 - 100 mg / kg; for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 mg / kg, or the range between any two of the foregoing values; preferably 20 - 50 mg / kg; or, The pathway regulator is etomidate or its pharmaceutically acceptable salt, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is emistat or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or a pharmaceutically acceptable salt thereof, and the unit dose is 80 - 120 mg / kg; for example, 80, 85, 90, 95, 100, 110, 120, or the range between any two of the foregoing values; preferably 90 - 110 mg / kg, more preferably 100 mg / kg. In the above drug composition, the drug composition may further contain one or more substances selected from chemotherapeutic agents, targeted therapeutic agents, immunotherapeutic agents, and anti-inflammatory agents. In the above drug composition, the drug is preferably used for one or more of the following uses: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, inhibiting the activation of B cells, and inhibiting the activation of NK cells. In the above drug composition, the pro-inflammatory factors of the CD4+ T cells are preferably one or more of IL-17A, IFN-γ, and TNF-α. In the above drug composition, the pro-inflammatory factors of the CD8+ T cells are preferably IL-17A and / or TNF-α. In the above drug composition, the regulatory T cells are preferably CD25+FOXP3+ Treg cells. In the above drug composition, the B cells are preferably B220+ cells, more preferably CD69+B220+ B cells. In the above drug composition, the NK cells are preferably NK1.1+ cells, more preferably NK1.1+CD107a+ NK cells. The positive effects of the present disclosure are as follows: The inventors found that DBH inhibitors can inhibit the occurrence and development of autoimmune diseases through immunomodulation (as an example, specifically reflected in the improvement of weight loss, the improvement of DAI scores, and the normalization of colon density), and thus can provide new options for the treatment of autoimmune diseases. Description of the Drawings Figure 1A shows the results of weight assessment of mice in each group after the experiment was conducted according to the experimental procedures described in Example 1. Figure 1B shows the results of DAI scores of mice in each group after the experiment was conducted according to the experimental procedures described in Example 1. Figure 1C shows the results of colon density of mice in each group after the experiment was conducted according to the experimental procedures described in Example 1. Figures 2A to 2E show the effects of CD4+ T cell subsets (Figure 2A), CD25+FOXP3+ Treg cell subsets (Figure 2B), IL-17A from CD4+ T cell subsets (Figure 2C), IFN-γ from CD4+ T cell subsets (Figure 2D), and TNF-α from CD4+ T cell subsets (Figure 2E) in the mesenteric lymph nodes of mice in each group in Example 4. Figures 3A to 3D show the effects of CD8+ T cell subsets (Figure 3A), IFN-γ from CD8+ T cell subsets (Figure 3B), IL-17A from CD8+ T cell subsets (Figure 3C), and TNF-α from CD8+ T cell subsets (Figure 3D) in the mesenteric lymph nodes of mice in each group in Example 4. Figures 4A to 4B show the effects of CD69+B220+ B cell subsets (Figure 4A) and NK1.1+CD107a+ NK cell subsets (Figure 4B) in the mesenteric lymph nodes of mice in each group in Example 4. In each of the above figures, * refers to p < 0.05, ** refers to p < 0.01, *** refers to p < 0.001, and **** refers to p < 0.0001. Figure 5 shows the weight changes in each group of Example 5; Two-way ANOVA: # p < 0.05, ### p < 0.001 vs. the vehicle group. Figure 6 shows the weight change rates in each group of Example 5. Figure 7 shows the spleen weights in each group of Example 5; One-way ANOVA: ***p < 0.001 vs. the normal group, #p < 0.05, ##p < 0.01 vs. the vehicle group. Figure 8 shows the visceral coefficients in each group of Example 5; One-way ANOVA: # p < 0.05, ## p < 0.01, ###p < 0.001 vs. solvent group. Figure 9 shows the peripheral blood red blood cell (RBC) count in each group of Example 5; One-way ANOVA: ***p < 0.001 vs normal group, ## p < 0.01, ### p < 0.001 vs solvent group, &&& p < 0.001 vs imatinib group. Figure 10 shows the peripheral blood hemoglobin (HGB) content in each group of Example 5; One-way ANOVA: ***p < 0.001 vs normal group, ## p < 0.01, ### p < 0.001 vs solvent group, &&& p < 0.001 vs imatinib group. Figure 11 shows the peripheral blood white blood cell (WBC) count in each group of Example 5; One-way ANOVA: *p < 0.05, ***p < 0.001 vs normal group, ## p < 0.01 vs solvent group. Figure 12 shows the peripheral blood lymphocyte (LYMPH) count in each group of Example 5; One-way ANOVA: # p < 0.05, ### p < 0.001 vs solvent group. Figure 13 shows the peripheral blood monocyte (MONO) count in each group of Example 5; One-way ANOVA: ## p < 0.01 vs solvent group. Figure 14 shows the peripheral blood neutrophil (NEUT) count in each group of Example 5; One-way ANOVA: ***p < 0.001 vs normal group. Figure 15 shows the peripheral blood platelet content in each group of Example 5; One-way ANOVA: ***p < 0.001 vs normal group, ### p < 0.001 vs solvent group, && p < 0.01, &&& p < 0.001 vs. nintedanib group, $$ p < 0.01 vs. imatinib group. Figure 16 shows the dermal inflammatory cell infiltration score in each group of Example 5; One-way ANOVA: # p < 0.05 vs. solvent group, $ p < 0.05 vs. nepicastat - 25 mg / kg, qd, po. Figure 17 shows the capillary density score in the dermis in each group of Example 5; One-way ANOVA:# p < 0.05, ## p < 0.01 vs. vehicle group. Figure 18 shows the dermal thickness in each group of Example 5; One-way ANOVA: *p < 0.05, **p < 0.01, ***p < 0.001 vs. normal group. Figure 19 shows the clinical scores in each group of Example 6. Figures 20A to 20D: Proportion of AQP4, GFAP, IBA1, and CD45 positive cells in each group of Example 7. Figure 21 shows the body weights of the animals in each group of Example 8. Figure 22 shows the AUC of the total score of erythema + scale + thickness in each group of Example 8; mean ± standard error, Two way ANOVA, compared with the corresponding vehicle group, p* < 0.05, p** < 0.01, p*** < 0.001, p**** < 0.0001 (Note: The AUC of the total score of the normal group is 0 and not shown in the figure). Figure 23 shows the spleen weights in each group of Example 8. Figure 24 shows the body weights of the animals in each group of Example 9. Figure 25 shows the clinical scores in each group of Example 9. Figure 26 shows the AUC in each group of Example 9. Figure 27 shows the incidence rates in each group of Example 9. Figure 28 shows the body weights of the animals in each group of Example 10. Figure 29 shows the rate of change in body weight of the animals in each group of Example 10. Figure 30 shows the fecal scores in each group of Example 10. Figure 31 shows the fecal score AUC in each group of Example 10. Figure 32 shows the changes in body weight in each group of Example 11. Figure 33 shows the DAI in each group of Example 11. Detailed implementation manners Various publications and patent applications are cited in the background art and throughout the specification; each of these references is incorporated herein by reference in its entirety. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Terms As used herein, the term "receptor agonist" refers to a substance that can act on the receptor of the substrate catalyzed by dopamine β-hydroxylase (i.e., dopamine) and exert the same mechanism and effect as the elevation of dopamine. The receptor agonist is preferably a dopamine receptor agonist. As used herein, the term "receptor antagonist" refers to a substance that can act on the receptors of the products catalyzed by dopamine β-hydroxylase (i.e., norepinephrine and / or epinephrine), and exerts the same mechanisms and effects as the reduction of norepinephrine and / or epinephrine. The receptor antagonist is preferably a norepinephrine receptor antagonist and / or an epinephrine receptor antagonist. The term "autoimmune disease" refers to a condition in which the body's own immune system attacks the body, characterized by the disruption of the adaptive immune tolerance mechanism for self / nonself recognition, and the abnormal response of adaptive immune cells leading to inflammatory damage of self-tissues. The term "dopamine β-hydroxylase" is intended to cover human dopamine β-hydroxylase, its fragments, variants, precursors, and functional domains. The term "DBH inhibitor" refers to any natural or artificial compound that can affect (this effect refers to reducing, decreasing, inhibiting, blocking, repressing, inactivating, or preventing activation) the structure, expression, or activity of dopamine β-hydroxylase at the nucleic acid or protein level. DBH inhibitors include those known in the prior art and those provided in the future. It includes the DBH inhibitors disclosed in CN87103323A and WO9529165, as well as nepicastat, etamicastat, zamicastat, fusaric acid, disulfiram, cysteamine, cysteamine derivatives, pantethine, and pantethine derivatives. The term "pharmaceutically acceptable carrier" refers to pharmaceutically acceptable excipients. The term "pharmaceutically acceptable salt" should be understood to refer to the following salts, which are pharmaceutically acceptable salts and possess the pharmacological activity of the expected parent compound. Such salts include: (1) Acid addition salts formed with inorganic acids or acid addition salts formed with organic acids; wherein, the inorganic acid can be one or more of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; the organic acid can be one or more of formic acid, oxalic acid, succinic acid, acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucic acid, 2-naphthalenesulfonic acid, propionic acid, salicylic acid, succinic acid, dibenzoyl-L-tartaric acid, tartaric acid, p-toluenesulfonic acid, trimethylacetic acid, and trifluoroacetic acid; and (2) the acid protons present in the parent compound are replaced by metal ions, such as, alkali metal ions (e.g., Na + , K + or Li + ), alkaline earth metal ions (such as Ca 2+ or Mg 2+) or replaced by aluminum ions; or, a salt formed when coordinating with an organic base or an inorganic base; wherein, the organic base can be one or more of pyridine-based, imidazole-based, pyrazine-based, indole-based, purine-based, tertiary amine-based, and aniline-based organic bases, preferably one or more of pyridine, methylpyridine, 4-dimethylaminopyridine, 2-methyl-5-ethylpyridine, triethylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, diethanolamine, ethanolamine, N-methylglucosamine, triethanolamine, and tromethamine; the inorganic base can be one or more of aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydroxide. The pharmaceutical composition of the present disclosure can be various conventional dosage forms, such as tablets, aqueous suspensions, oily suspensions, dispersible powders, dispersible granules, emulsions, hard capsules, soft capsules, sterile injectable aqueous solutions, sterile water-in-oil microemulsions, or suppositories. Each of the above dosage forms can be prepared by conventional preparation methods. The excipients in the tablets of the present disclosure can be one or more of fillers, binders, lubricants, glidants, and disintegrants. Among them, the filler can be one or more of microcrystalline cellulose, starch, lactose monohydrate, and calcium hydrogen phosphate. The binder can be one or more of starch, gelatin, polyvinylpyrrolidone, and gum arabic. The lubricant can be one or more of magnesium stearate, stearic acid, and sodium lauryl sulfate. The glidant can be one or two of colloidal silicon dioxide and talc powder. The disintegrant can be one or more of crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked carboxymethyl cellulose sodium. The tablets can also contain a coating. The tablets can also be made into sustained-release preparations, and the sustained-release materials in the sustained-release preparations can be one or two of hydroxypropyl methylcellulose and xanthan gum. The excipients in the aqueous suspensions of the present disclosure can be one or more of suspending agents, dispersants, preservatives, and flavoring agents. Among them, the suspending agent can be one or more of sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methylcellulose, sodium alginate, polyvinylpyrrolidone, and gum arabic. The dispersant can be one or more of naturally occurring phospholipids (such as lecithin), condensation products of ethylene oxide and fatty acids (such as polyoxyethylene stearate), condensation products of ethylene oxide and long-chain fatty alcohols (such as heptadecethyleneoxy cetyl alcohol), condensation products of ethylene oxide and partial esters derived from fatty acids and hexitols (such as polyoxyethylene sorbitan monooleate), and condensation products of ethylene oxide and partial esters derived from fatty acids and hexitol anhydrides (such as polyoxyethylene sorbitan monooleate). The preservative can be ethyl paraben and / or propyl paraben. The flavoring agent can be one or more of sucrose, saccharin, and aspartame. The excipients in the oil suspension of the present disclosure may be one or more of a suspending agent, a thickening agent, a flavoring agent, and an antioxidant. The suspending agent may be a vegetable oil and / or a mineral oil. The vegetable oil may be one or more of peanut oil, olive oil, sesame oil, and coconut oil. The mineral oil may be liquid paraffin. The thickening agent may be one or more of beeswax, hard paraffin, and cetyl alcohol. The flavoring agent may be one or more of sucrose, saccharin, and aspartame. The antioxidant may be one or more of butylated hydroxyanisole, α-tocopherol, and ascorbic acid. The excipients in the dispersible powder and the dispersible granule of the present disclosure may be one or more of a suspending agent, a dispersing agent, a preservative, a flavoring agent, and an antioxidant. The specific selection of each of the above components is the same as that of the excipients in the aqueous suspension. The excipients in the emulsion of the present disclosure may be one or more of a suspending agent, an emulsifying agent, a flavoring agent, a preservative, and an antioxidant. The suspending agent may be a vegetable oil and / or a mineral oil. The vegetable oil may be olive oil and / or peanut oil. The mineral oil may be liquid paraffin. The emulsifying agent may be one or more of naturally occurring phospholipids (such as soybean lecithin), esters or partial esters derived from fatty acids and sorbitan anhydride (such as sorbitan monooleate), and condensation products of the partial esters and ethylene oxide (such as polyethylene oxide sorbitan monooleate). The flavoring agent may be one or more of glycerol, propylene glycol, sorbitol, and sucrose. The preservative may be ethyl paraben and / or propyl paraben. The antioxidant may be one or more of butylated hydroxyanisole, α-tocopherol, and ascorbic acid. The excipients in the hard capsules of the present disclosure may be conventional inert solid diluents, such as one or more of calcium carbonate, calcium phosphate, and kaolin. The excipients in the soft capsules of the present disclosure may be conventional water-soluble carriers and / or conventional oil solvents, such as one or more of polyethylene glycol, peanut oil, liquid paraffin, and olive oil. The excipients in the sterile injectable aqueous solution of the present disclosure may be pharmaceutically acceptable solvents, such as water, Ringer's solution, or isotonic sodium chloride solution. The excipients in the sterile oil-in-water microemulsion for injection of the present disclosure may be oil-phase excipients and water-phase excipients. The oil-phase excipients may be a mixture of soybean oil and lecithin. The water-phase excipients may be a mixture of water and glycerol. The excipients in the suppositories of the present disclosure may be one or more of cocoa butter, glycerol, gelatin, hydrogenated vegetable oil, polyethylene glycol, and fatty acid esters of polyethylene glycol. The term "subject" refers to an animal, preferably a mammal. According to specific embodiments, the subject is a mammal, including, for example, camels, donkeys, zebras, cows, pigs, horses, goats, sheep, cats, dogs, rats, rabbits, guinea pigs, mice, primates (such as humans). In a specific embodiment, the subject is a human. In a specific embodiment, the subject is a human susceptible to, suspected of having, or having an autoimmune disease. The term "treatment" refers to eliminating a disease, preventing the progression of a disease, slowing the progression of a disease, reducing the duration of one or more symptoms associated with a disease, improving or reversing at least one measurable parameter associated with a disease, or increasing the survival rate of a subject having the disease. The term "effective amount" refers to the amount of a pharmaceutically active ingredient that elicits a desired effect in a subject. In specific embodiments, those skilled in the art can determine the selection of the effective amount based on consideration of a variety of factors (such as via clinical trials), including the disease to be treated, the symptoms involved, the route of administration, the severity of the disease, the weight of the patient, the immune status of the patient, and other factors known to those skilled in the art. The effective amount in a specific embodiment can be obtained from a dose-response curve from an animal model test system and allows for determination based on the judgment of a physician and the circumstances of each patient. Among them, the relationship between the drug dosages for animals and humans is described in Freireich et al. 1966, Cancer Chemother Rep 50:219, and the body surface area of a human can be approximately determined from the height and weight of the patient. The effective amount of the pharmaceutical compounds of the present disclosure can be 0.5 mg / kg to 500 mg / kg, preferably 1 mg / kg to 200 mg / kg, more preferably 10 mg / kg to 100 mg / kg. In this document, the same pharmaceutically active ingredient (referring to a single pharmaceutical compound) or different pharmaceutically active ingredients (referring to two or more pharmaceutical compounds) can be administered once, or can be divided into many smaller unit doses and administered at regular time intervals. It should be understood that the exact dosage, duration, and interval of treatment are a function of the disease being treated and can be determined by extrapolation using animal or clinical trial data. The administration can include a single administration, or two or more administrations at appropriate time intervals. Among them, the interval between two adjacent administrations can be 30 minutes, 40 minutes, 50 minutes, 60 minutes, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, one and a half days, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months. Each active pharmaceutical ingredient (each pharmaceutical compound) mentioned in this article can be used as the sole active compound or can be administered in combination with other active compounds (compounds other than the pharmaceutical compounds described in this article), as long as they do not produce other adverse effects, such as allergic reactions, etc. The combined administration includes administering each active compound simultaneously or successively. The term "combined administration" refers to a method of providing two or more active compounds to a subject simultaneously or successively for the purpose of achieving a therapeutic effect. When "combined administration" is involved, the time interval between each administration is sufficient to achieve a synergistic effect between the administered active compounds. The two or more active compounds are in the same or different containers. Abbreviations: QD: once a day; BID: twice a day; PO: oral; IP: intraperitoneal injection; IM: intramuscular injection. Example 1: Inhibitory effect of DBH inhibitor on dextran sulfate sodium (DSS)-induced colitis 1. Materials and equipment: Table 1. Reagents Reagent Supplier Catalog number Dulbecco's Phosphate Buffered Saline (1×DPBS) Corning Incorporated 21-031-CVR Dextran sulfate sodium (DSS) MP Biomedicals SR01606 Cyclosporin A (CsA) Novartis / Normal saline Ke Lun Pharmaceutical Co., Ltd / PEG400 Sigma Aldrich 25322-68-3 30% Solutol HS15 Sigma Aldrich 70142-34-6 Nepicastat Selleckchem S2695 Etamicastat Nanjing Pharmaron 677773-32-9 Emicastat MCE 1080028-80-3 Table 2. Instruments Instrument Supplier Model Electronic balance Changzhou Tianzhiping YH-2000 Electronic analytical balance Mettle Toledo 585310 2. Preparation and storage of the drug solution: The composition of the solvent is as follows: 20v% PEG400 + 10v% (30% Solutol HS15) + 70v% normal saline. Test substance - Nepicastat drug solution: 27 mg of Nepicastat was completely dissolved in 9 mL of the solvent (this concentration corresponds to test group 1#), prepared every 3 days, and stored at 4°C to maintain the effect. Test substance - Etamicastat solution: Dissolve 9 mg, 27 mg, and 90 mg of etamicastat in 9 mL of solvent respectively (the three concentrations correspond to Test Group 2#, Test Group 3#, and Test Group 4#). Prepare the solution every 3 days and store it at 4°C to maintain the effect. Test substance - Emisat solution: Dissolve 9 mg, 27 mg, and 90 mg of emisat in 9 mL of solvent respectively (the three concentrations correspond to Test Group 5#, Test Group 6#, and Test Group 7#). Prepare the solution every 3 days and store it at 4°C to maintain the effect. Positive drug control - Cyclosporine A solution: Dissolve 200 mg of cyclosporine A in 10 mL of physiological saline to prepare a 20 mg / mL solution (corresponding to the positive drug control group). Prepare the solution every 3 days and store it at 4°C to maintain the effect. 3. Treatment of mice in each group: Use 8 - 10 - week - old female C57BL / 6J mice purchased from Vital River Laboratories (Charles River Laboratories). In a room with a constant temperature of (20 ± 2)°C (5 mice per cage), a 12 - hour light - dark cycle is carried out. All experimental protocols have been approved by the Institutional Animal Care and Use Committee of WuXi AppTec. Before the experiment, these mice were acclimatized in the animal experiment center of WuXi AppTec for at least three days. (1) Solvent group, positive drug control group, and test groups To establish a dextran sulfate sodium - induced colitis model, freely drink a 3% DSS aqueous solution for 7 consecutive days (prepared by adding 3 g of DSS to 100 mL of water, where the molecular weight of DSS is 36000 - 50000) to induce colitis (this colitis belongs to autoimmune colitis), and divide them into 9 groups for administration respectively (the solvent group, positive drug control group, and Test Group 1# to Test Group 7# in Table 3), where the 3% DSS aqueous solution is freshly prepared every day. At the end of the experiment (see below), they were euthanized and terminal samples were obtained. (2) Normal group The mice in the normal group were not induced with colitis by the 3% DSS aqueous solution, but freely drank blank water. At the end of the experiment (see below), they were euthanized and terminal samples were obtained. Table 3. Groups and dosing regimens 4. Body weight assessment and disease activity index (DAI) scoring: The animal body weight and DAI score were measured under double-blind conditions, that is, the researchers were unaware of the group and drug administration. The body weight of the mice was collected daily, and the stool characteristics, bloody stools were observed and scored. The DAI score is the sum of the body weight loss score, defecation score and bleeding score. The scoring criteria are shown in Table 4. Table 4. DAI Scoring System 5. Statistical Analysis: Analysis of variance was used for data analysis, and the specific method was as follows: Graph Pad Prism 6.0 software was used, and the post-hoc Dunnett's multiple comparison test method was adopted. The remaining groups (referring to the normal group, positive drug control group and test groups 1# to 7#) were compared with the vehicle group to analyze whether there was a significant difference between the remaining groups and the vehicle group. If the p-value < 0.05, there was a statistically significant difference, which was significant. The data was expressed as mean ± S.E.M. Example 2: Effects of DBH Inhibitor on Immune Cell Activation and Cytokines 1. Materials: Table 5. Flow Cytometry Antibody Reagents Table 6. Other Reagents 2. Methods: For the positive drug control group and test groups 1# to 7# in Example 1, 24 hours after drug administration on the 8th day was the experimental end point; the experimental end points of the normal group and the vehicle group were the same as those of the positive drug control group and test groups 1# to 7#. At the experimental end point, the mesenteric lymph nodes were collected and processed as follows: 1) Gently grind the mesenteric lymph nodes, filter them through a 70 μM filter (BD bioscience, catalog number 352350) to obtain a cell suspension, and count the cells. 2) Suspend the cells with a suspension (prepared by diluting the cell activation mixture with a mixture composed of 90 v% 1640 medium and 10 v% fetal bovine serum to a concentration of 1×), adjust the cell density to 2.5×10 7 / mL, and incubate at 37 °C for 5 hours. 3) Wash the cells with Dulbecco's phosphate buffered saline, stain with a viable / dead dye (dye No. 12 in Table 5) at room temperature for 15 min to distinguish viable cells from dead cells; wash the cells with staining buffer (prepared by mixing fetal bovine serum and Dulbecco's phosphate buffered saline at a volume ratio of 2:98), add the Fc blocker working solution (prepared by mixing Fc blocker and staining buffer at a volume ratio of 1:200), and incubate at room temperature for 15 minutes. 4) Without washing the cells, label the cells on the surface with 100 μL of flow cytometry antibody staining solution and incubate at 4 °C for 30 minutes. 5) Wash the cells once with staining buffer, add 100 μL of cell fixative, and incubate at 4 °C overnight. 6) Add 200 μL of cell permeabilization solution and incubate at 4 °C for 30 minutes. 7) After washing the cells with 250 μL of cell permeabilization wash solution, resuspend the cells with 100 μL of staining buffer and detect the fluorescence with a BD LSRFortessa instrument. 8) The cell subsets for flow cytometry analysis include CD4+ T cell subset, IL-17A+ CD4+ T cell subset, IFN-γ+ CD4+ T cell subset, TNF-α+ CD4+ T cell subset, CD25+ FOXP3+ Treg cell subset; CD8+ T cell subset, IL-17A+ CD8+ T cell subset, IFN-γ+ CD8+ T cell subset, TNF-α+ CD8+ T cell subset; CD69+ B220+ B cell subset and NK1.1+ CD107a+ NK cell subset. Example 3: The DBH inhibitor improved DSS-induced colonic injury After conducting the experiment according to the experimental procedure described in Example 1, the results of body weight assessment of mice in each group are shown in Table 7 and Figure 1A; the results of DAI scores of mice in each group are shown in Table 8 and Figure 1B; the results of colon density of mice in each group are shown in Table 9 and Figure 1C. Compared with the vehicle group, the weight loss of mice in test groups 1#, 4# and 7# was significantly reduced on the 7th day of treatment (Figure 1A, Table 7). Compared with the vehicle group, the DAI scores of mice in test groups 1#, 2#, 3#, 4#, 5#, 6# and 7# were significantly reduced on the 7th day of treatment (Figure 1B, Table 8). After mice were given DSS, it usually led to colon shortening and increased colon density. These two indicators could reflect the severity of DSS-induced colitis. Compared with the vehicle group, the colon density in test groups 1#, 4# and 7# was significantly decreased (Figure 1C, Table 9). These data indicated that nepicastat, etomoxastat and imoxastat improved the severity of DSS-induced colitis and reduced the disease activity. In summary, DSS-induced colitis in test groups 1#, 4# and 7# was milder than that in the vehicle group, suggesting that nepicastat, etomoxastat and imoxastat have potential therapeutic effects on colitis. Example 4: Effects of Nepicastat and Imoxastat on Immune Cells and Cytokines According to the method of Example 2, the effects of nepicastat and imoxastat on immune cells and cytokines were analyzed. The obtained results are shown in Figures 2A to 2E, Figures 3A to 3D, and Figures 4A to 4B. First, the changes in the CD4+ T cell subset from the CD3+CD45+ cell subset were analyzed, and the changes in the CD25+FOXP3+ Treg cell subset from the CD4+ cell subset were also analyzed. The results showed that compared with the vehicle group, in test groups 1# and 7#, the proportion of the CD4+ T cell subset could be decreased (Figure 2A), while the proportion of the CD25+FOXP3+ Treg cell subset was increased (Figure 2B). The above results suggested that the DBH inhibitor could significantly inhibit inflammation and immunity. Then, the cytokines secreted by the CD4+ T cell subset were further analyzed. The results showed that compared with the vehicle group, in test groups 1# and 7#, the secretion of pro-inflammatory factors IL-17A (Figure 2C), IFN-γ (Figure 2D) and TNF-α (Figure 2E) could be decreased, further suggesting that the DBH inhibitor exerted the role of inhibiting inflammation and immunity by reducing the secretion of pro-inflammatory factors by the CD4+ T cell subset. In addition, a similar analysis was performed on the CD8+ T cell subset from the CD3+CD45+ cell subset and the cytokines it secreted. The results showed that compared with the vehicle group, the DBH inhibitor could increase the proportion of the CD8+ T cell subset (Figure 3A), had no significant effect on the secretion of IFN-γ (Figure 3B), but could inhibit the secretion of IL-17A (Figure 3C) and TNF-α (Figure 3D). The above results suggested that the DBH inhibitor inhibited inflammation and immunity by reducing the secretion of IL-17A and TNF-α by the CD8+ T cell subset. Finally, the activation of B cells (referring to the CD69+ B220+ B cell subset from the CD3- cell subset) and NK cells (referring to the NK1.1+ CD107a+ NK cell subset from the CD3- B220- cell subset) was evaluated. The results showed that compared with the vehicle group, DBH inhibitors could inhibit the activation of B cells (Figure 4A) and NK cells (Figure 4B). The above results suggest that DBH inhibitors can reduce the risk of B cells producing autoantibodies and the non-specific killing of mucosal tissues mediated by NK cells, thereby alleviating inflammation and inhibiting immunity. Example 5: Inhibitory Effect of DBH Inhibitor on Bleomycin-Induced Skin Fibrosis in Male C57 Mice 1. Materials and Equipment Table 10. Reagents Reagent Supplier Catalog Number Normal saline Zhejiang Dubang Pharmaceutical Co., Ltd. 2009240101 Solutol HS15 Sigma BCCF2234 PEG400 Sinopharm Chemical Reagent Co., Ltd. 20181205 MC Sigma SLBT4343 Tween 80 Sigma WXBD2914 Isoflurane RWD Reworld 20120101 Bleomycin Hydrochloride Nippon Kayaku Co., Ltd. 600700 Table 11. Instruments Name Model and Manufacturer Respiratory anesthesia machine AMS (Gene&I) Beijing Jiandel Technology Co., Ltd. (Jiandel) Automatic blood analyzer Sysmex XS-800i Tissue dehydrator LEICA HistoCore Pearl Embedding machine Leica Histocore Arcadia C&H Microtome LEICA, RM2235 Automatic stainer LEICA, ST5020 Slide scanner HAMAMATSU Nano Zoomer S210 CNC ultrasonic cleaner KQ-100DE, Kunshan Ultrasonic Instrument Co., Ltd. 2. Preparation and Storage of Pharmaceutical Solutions Composition of the vehicle: 20% PEG400 + 10% (30% Solutol HS15) + 70% normal saline. Measure 100 mL of PEG400 and 50 mL of 30% (V / V) solutol, add them to 350 mL of normal saline; place on a magnetic stirrer and stir until evenly mixed, and store at 4°C for later use. Test substance - Nepicastat liquid: Weigh 40 mg of the test substance into a brown sample vial, add 0.8 mL of PEG400, vortex on a vortex mixer, sonicate for 15 minutes, heat in a water bath at 40 °C for 15 minutes to form a suspension, then add 0.4 mL of 30% Solutol HS15, vortex on a vortex mixer to mix evenly, and then add 2.8 mL of normal saline, vortex on a vortex mixer to mix evenly until a solution is formed, with a compound concentration of 10 mg / mL. Prepare it every three days and store it at 4 °C for later use. Reference substance - Nintedanib liquid: Accurately weigh 25 mg of nintedanib (BIBF1120), add it to 5 mL of solvent (0.5% MC + 0.2% Tween80), mix well until the solution is clear and transparent, with a drug concentration of 5 mg / mL (the dosing dose is 10 mL / kg). Prepare it every seven days. Reference substance - Imatinib liquid: Accurately weigh 15 mg of imatinib mesylate powder into a sample vial, add 3 mL of normal saline, vortex on a vortex mixer until completely dissolved, with a drug concentration of 5 mg / mL. Prepare it immediately before use and use it up within half an hour. 3. Test method 3.1 Animal feeding 70 male C57BL / 6 mice (weighing 20 to 22 g) are housed in the SPF - level barrier system of Kaiseai Biotechnology (Suzhou) Co., Ltd. The animal use certificate number is: SYXK (Su) 2017 - 0041, and they follow the international standard temperature, humidity, and light control system. The animal operation plan for this experiment has been jointly approved and confirmed by the IACUC committee. The operation and management are strictly carried out in accordance with the SOP of Kaiseai Biotechnology (Suzhou) Co., Ltd. 3.2 Model establishment The animals are anesthetized with isoflurane (2.0 to 2.5%), the hair on the back is removed, and a bleomycin (0.3 mg / kg, 100 μL) intradermal injection is performed every two days on an area of 1 cm 2 area to establish a skin fibrosis model. 3.3 Test grouping According to the animal body weight, they are divided into 7 groups, with 10 animals in each group, namely: normal group, solvent group, nintedanib group (positive control drug), imatinib (positive control drug), test group 1#, test group 2#, and test group 3#. The specific situation is shown in Table 12. Table 12. Test grouping and dosing plan Note: a: 20% PEG400 + 10% (30% Solutol HS15) + 70% normal saline. 3.4 Test dosing The start time of drug administration was the day of model establishment. Before each animal was administered the drug, its body weight was measured to calculate the drug administration volume. The drug administration period was 28 days. Drug administration method: The imatinib group was administered by intraperitoneal injection, and the remaining groups were administered by gavage. Drug administration frequency: The nintedanib group was administered twice a day, and the remaining groups were administered once a day. 3.5 Physiological Observation of Experimental Animals From the day of model establishment, the body weight changes of the animals were recorded twice a week; the clinical manifestations of the animals were closely observed, such as shortness of breath, difficulty breathing, abdominal retraction, decreased activity, listlessness, etc. 3.6 Local Skin Observation At the end of the experiment, the animals were euthanized by intraperitoneal injection of an overdose of pentobarbital sodium (100 mg / kg), and then local skin photos were taken. 3.7 Endpoint of the Experiment At the end of the experiment, the animals were weighed and recorded, and the drug administration volume was calculated. 6 hours after drug administration, first, whole blood was taken from the orbital venous plexus of the mice, and routine blood tests were performed using an automatic hematology analyzer (Sysmex XS-800i). The specific detection steps were as follows: Before detection, the blood samples in the test tubes were thoroughly mixed; the samples were placed under the sampling needle, and then the start button was pressed to sample. After the instrument indicator light went out, the samples were removed; the instrument started to automatically detect and output the results. Then the animals were anesthetized with pentobarbital sodium by intraperitoneal injection for euthanasia. The content and order of anatomical sampling were as follows: The spleen was taken, weighed and recorded. The bilateral inguinal lymph nodes were taken, frozen quickly and stored in a -80 °C refrigerator. For the diseased skin tissue, first, skin images were collected, and then it was immersed in 10% formalin fixative for fixation. The ratio of tissue to formalin was 1:10. After fixation for 48 hours, histopathological detection was performed. The specific content is shown in Table 13 below. Table 13. Endpoint of the Experiment 3.8 Histopathological Detection According to the pathological SOP, the diseased skin was dehydrated, embedded and sectioned, and the tissues were stained with HE and Masson. The histopathological analysis was performed according to the following method: 3.8.1 Dermal Thickness The sections stained with Masson were panoramically scanned with Nanozomer S210, and the scanned images were quantitatively analyzed using Visiopharm VIS6.0 software. The degree of fibrosis is currently represented by the dermal thickness after Masson staining. 3.8.2 Scoring of Capillary Density in the Dermis Observation fields were selected in the dermis of the lesion area (the number of fields selected was determined according to the size of the lesion area), and the capillary density was scored according to the area occupied in this region: 0: No capillary angiogenesis was seen 1: The proportion of angiogenesis is less than 25%; 2: The proportion of angiogenesis is 25 - 50%; 3: The proportion of angiogenesis is 50 - 75%; 4: The proportion of angiogenesis is greater than 75%. 3.8.3 Dermal inflammatory cell infiltration score Select the observation fields in the dermis of the lesion area (determine how many fields to select according to the size of the lesion area), and score according to the degree of inflammatory cell infiltration: 0: No inflammatory cell infiltration is seen; 1: A small amount of focal inflammatory cell infiltration; 2: Scattered and diffuse inflammatory cell infiltration; 3: A large amount of diffuse inflammatory cell infiltration 4: A large amount of inflammatory cells aggregated into groups. 3.9 Data analysis Use Graphpad prism 6.0 software to calculate the mean ± SEM. For the significance test of differences, use t-test, one-way ANOVA test or two-way ANOVA test. When p < 0.05, it is considered that there is a significant difference between the two groups. 4 Experimental results 4.1 Body weight changes During the experiment, the body weight of the animals in the normal group showed an upward trend. The body weights of Detection Group 1#, Detection Group 2#, and Detection Group 3# remained stable and fluctuated within the normal range. Only the nintedanib group and the imatinib group showed a slow decreasing trend after drug administration, and there was always a significant difference compared with the vehicle group during the period from the 25th to the 28th day (see Figures 5 and 6 below). One animal in the imatinib group died on the 28th day, and the body weight on the day of death decreased by 23.7% compared with the body weight before modeling. 4.2 Spleen and visceral coefficients At the end of the experiment, take the spleen, weigh the spleen weight and calculate the visceral coefficient (spleen / body weight × 100%). The results are shown in Figure 7. The spleen weight of the vehicle group decreased significantly compared with the normal group. The spleen weights of the nintedanib group, the imatinib group, Detection Group 1#, Detection Group 2#, and Detection Group 3# also decreased significantly compared with the vehicle group. In terms of the spleen visceral coefficient, there was no obvious difference between the vehicle group and the normal group, indicating that the spleen visceral coefficient of the mice could not be changed after modeling. Only the nintedanib group, Detection Group 1#, Detection Group 2#, and Detection Group 3# had a significant difference compared with the vehicle group (Table 14, Figure 8). Table 14. Spleen weight and visceral coefficient ***p < 0.001 vs. normal group, # p < 0.05, ## p < 0.01 vs. solvent group. 4.3 Blood routine Peripheral blood was collected at the end of the experiment for blood routine tests. The results showed that imatinib significantly reduced the content of red blood cells and hemoglobin in peripheral blood, which was also consistent with the anemia symptoms of the animals in this group at the end of the experiment. In addition, imatinib could significantly reduce the content of white blood cells in peripheral blood (including lymphocytes and neutrophils); there was a tendency to decrease in monocytes, but there was no significant difference. Compared with the solvent group, there were significant differences in reducing lymphocytes, neutrophils and monocytes in test group 3#, indicating that the treatment with the dose of 100 mg / kg in test group 3# had an anti-inflammatory effect, which was consistent with the pathological results (Figs. 9 to 15). 4.4 Skin pathological staining results Systemic sclerosis (SSc) is an autoimmune disease, manifested as inflammation, vascular lesions, skin and organ fibrosis. In this example, bleomycin (BLM) was used to establish a mouse fibrosis model. The pathological HE staining results showed that compared with the solvent group and the normal group, there were significant inflammatory cell infiltrations and dermal capillary hyperplasia; the Masson staining results showed that the animals in the solvent group had a stronger degree of skin fibrosis and a significant increase in dermal thickness. The treatments with nintedanib and imatinib could significantly reduce the inflammatory cell infiltration and dermal capillary hyperplasia in the lesioned skin. Test group 2# and test group 3# could significantly reduce the inflammatory cell infiltration and dermal capillary hyperplasia in the dermis. According to the statistical results of dermal thickness, the effects of the three different doses of penstilat in the test substance on reducing dermal thickness were progressive, and the higher the dose, the more obvious the reduction result, but there was no significant difference compared with the model group. Compared with test group 1# and test group 2#, test group 3# had a better effect on improving skin fibrosis (Figs. 16 to 18). From the above test results, it can be seen that test group 2# and test group 3# can reduce the increased number of inflammatory cell responses in peripheral blood after bleomycin stimulation, and reduce the inflammatory cell infiltration and capillary hyperplasia in the dermis of the lesioned skin. Especially, the effect of the 100 mg / kg dose corresponding to test group 3# is the best, and 100 mg / kg can also reduce the degree of skin fibrosis in the lesioned skin. Example 6: Effects of DBH inhibitor on experimental autoimmune uveoretinitis (EAU) induced by bovine IRBP R16 in Lewis rats 1. Materials and equipment Table 15. Reagents Table 16. Equipment Equipment Manufacturer Model Tissue Processor Fisher / Thermo A78400006 Tissue Embedding Machine Fisher / Thermo B64100010 2. Preparation and Preservation of Liquid Medicine Test Substance - Nepicastat Liquid Medicine: Taking the preparation of 10 mg / mL nepicastat liquid medicine as an example: Weigh 40 mg of nepicastat into a brown sample bottle, add 0.8 mL of PEG400, vortex on a vortex mixer, ultrasonicate for 15 minutes, heat in a water bath at 40 °C for 15 minutes to form a suspension, then add 0.4 mL of 30% Solutol HS15, vortex the suspension, and then add 2.8 mL of normal saline and vortex completely until a solution is formed. Prepare and use it freshly every day. Reference Substance - Dexamethasone Liquid Medicine: Suspend dexamethasone in sodium carboxymethylcellulose with a mass concentration of 0.5%, and the concentration is 0.04 mg / mL. Prepare and use it freshly every day. IRBP R16 Solution: Dissolve bovine IRBP R16 polypeptide in normal saline to a final concentration of 300 μg / mL. Complete Freund's Adjuvant (CFA): Mix 15 mg of Mycobacterium tuberculosis H37Ra with 10 mL of CFA, and the final concentration is 2.5 mg / mL (CFA itself contains 1.5 mg / mL of H37Ra, add 15 mg of H37Ra to 10 mL of CFA, and the final concentration is 2.5 mg / mL). Preparation of Emulsion: The emulsion is prepared by the method of manual mixing. First, take two 10 mL syringes. One syringe is filled with 4 mL of 300 μg / mL IRBP R16 solution and connected to a three-way stopcock valve to ensure that all air bubbles are removed. Then connect a syringe containing 4 mL of CFA and start mixing quickly. Manually mix by pushing the plunger back and forth for 5 minutes. Finally, use another 10 mL syringe to draw 8 mL of emulsion, then connect a large-bore needle (such as 18g), insert the needle into the end of a 1 mL syringe, and dispense the emulsion into 10 1 mL syringes. At the same time, when the needle is put on the syringe, the plunger can be pushed back and forth to ensure that there are no air bubbles. The emulsion should be used within 3 hours after preparation. 3. Test Methods The test rats are 6 - 8-week-old female Lewis rats purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., weighing about 180 - 220 g, and are free of specific pathogens at the start of the experiment. They are placed in a room at room temperature (20 - 26 °C, relative humidity 40 - 70%) with a 12 / 12-hour light / dark cycle (2 - 4 rats per cage). All experimental protocols have been approved by the IACUC (Institutional Animal Care and Use Committee) of Pengli Biotechnology. Before the experiment, the test rats are acclimated in the Pengli Biotechnology laboratory for 7 days. (1) Immunize rats with IRBP R16 emulsion On day -1 (i.e., the day before immunization, the same below), 60 rats were randomly divided into 6 groups (n = 10) according to body weight (see Table 18). On day 0, rats in groups 2 to 6 were anesthetized with isoflurane and then subcutaneously injected with a total of 200 mL of an emulsion obtained by emulsifying IRBP R16 and CFA at a ratio of 1:1 v / v, respectively, at two thighs (50 μL at each site) and the root of the tail (100 μL). Among them, day 0 refers to the day of immunization. The body weight of each rat was monitored twice a week after immunization. (2) Clinical evaluation of EAU in rats Starting from day 0 after immunization, the upper and lower eyelids of the rats' eyes were gently separated, and the rats' eyes were examined with a flashlight every day to record the incidence of the disease. According to the criteria listed in Table 17, the clinical symptoms were scored blindly from the onset of the disease to the end of the study. Table 17. Clinical scoring of EAU in rats Scoring criteria 0 No disease; eyes translucent and reflecting light (red reflex) 0.5 (trace) Iris vascular dilation 1 Iris vascular filling; abnormal pupil constriction 2 Blurred anterior chamber; reduced red reflex 3 Moderately opaque anterior chamber, but the pupil is still visible; dark red reflex 4 Turbid anterior chamber, blurred pupil; absent red reflex; exophthalmos (3) Drug administration regimen Drug administration started from day 0, and the drug was administered precisely according to the animal's body weight for a total of 16 days. The drug administration regimen for the test rats is shown in Table 18. Table 18. Drug administration regimen a: 20% PEG400 + 10% (30% Solutol HS15) + 70% normal saline b: 0.5% sodium carboxymethylcellulose. (4) Statistical analysis of experimental results The results are expressed as "mean ± standard error". Statistical analysis was performed using Graphpad Prism or SPSS, and p < 0.05 was considered statistically significant. 4. Test results (1) Body weight of rats The changes in the body weight of the test rats are shown in Table 19 below, presented as mean and standard error, respectively. Table 19. Body weight of rats (g) Mean - Day - 1 Day - 2 Day - 6 Day - 9 Day - 13 Day - 16 Blank Control 195.89 198.20 209.00 215.42 216.80 221.80 Model Control 186.99 192.94 200.05 204.24 209.85 210.04 Dexamethasone 188.46 174.65 166.65 164.05 162.10 161.29 NPI - 0052 (25mpk) 188.31 193.95 204.67 207.81 214.28 219.00 NPI - 0052 (50mpk) 189.34 194.04 202.28 206.07 216.20 218.42 NPI - 0052 (100mpk) 189.92 194.02 205.97 214.36 223.98 227.40 Standard Error - Day - 1 Day - 2 Day - 6 Day - 9 Day - 13 Day - 16 Blank Control 2.77 2.32 1.97 2.84 2.62 3.28 Model Control 2.49 1.87 2.47 2.33 2.98 2.84 Dexamethasone 2.41 1.66 2.19 2.29 3.13 3.27 NPI - 0052 (25mpk) 2.55 2.13 2.94 2.31 2.50 3.23 NPI - 0052 (50mpk) 2.61 2.21 2.14 3.36 3.39 2.81 NPI - 0052 (100mpk) 2.72 3.82 3.38 3.85 3.28 3.86 (2) Weight Change Rate Table 20. Weight Change Rate (%) Mean - Day 1 - Day 2 - Day 6 - Day 9 - Day 13 - Day 16 Blank control 0.00% 3.47% 7.84% 9.71% 11.59% 13.89% Model control 0.00% 3.25% 7.06% 9.26% 12.23% 12.36% Dexamethasone 0.00% - 7.26% - 11.53% - 12.92% - 13.99% - 14.44% NPI - 005 (25mpk) 0.00% 3.25% 7.06% 9.26% 12.23% 12.36% NPI - 005 (50mpk) 0.00% 2.53% 6.90% 8.83% 14.24% 15.41% NPI - 005 (100mpk) 0.00% 2.11% 8.45% 12.84% 17.96% 19.77% Standard error - Day 1 - Day 2 - Day 6 - Day 9 - Day 13 - Day 16 Blank control 0.00% 0.61% 0.88% 0.78% 0.76% 0.81% Model control 0.00% 0.72% 1.24% 0.60% 0.75% 0.95% Dexamethasone 0.00% 0.92% 0.91% 0.91% 1.28% 1.18% NPI - 005 (25mpk) 0.00% 0.72% 0.84% 0.87% 1.20% 1.06% NPI - 005 (50mpk) 0.00% 0.61% 0.81% 0.87% 1.48% 1.05% NPI - 005 (100mpk) 0.00% 0.97% 0.88% 0.84% 0.89% 1.46% (3) Clinical score See Figure 19 and Table 21. Table 21. Area under the curve (AUC) of clinical score a: Inhibition rate = [AUC (model control) - AUC (test group)] / AUC (model control), and the test group includes the dexamethasone group and the NPI - 005 group. (4) Incidence Table 22. Incidence (%) The successful establishment of the rat uveitis model can be demonstrated by the increase in the EAU clinical score. The treatment with NPI - 005 can slightly improve the symptoms of uveitis, reducing the EAU clinical score and the AUC of the clinical score, but this effect did not reach statistical significance. The inhibition rates of NPI - 005 on the AUC of the clinical score at doses of 25, 50, and 100 mg / kg were 8.67%, 20.06%, and 24.09% respectively. As a positive control, the clinical score and the AUC of the clinical score of uveitis were significantly reduced by dexamethasone treatment, and the inhibition rate on the AUC of the clinical score was 84.53%. Example 7: Effect of DBH inhibitor on neuromyelitis optica (NMO) induced by NMO-IgG in mice 1. Materials and equipment Table 23. Reagents Table 24. Equipment Equipment Manufacturer Model RWD Stereotaxic Instrument for Brain RWD Life Science Co., Ltd. 68025 Kd Scientific Syringe Pump Kd Scientific legato130 Hamilton Microsyringe Hamilton Gastight #1702 Disposable Threaded Suture Needle Ningbo Medical Suture Needle Co., Ltd. Angular Needle 3 / 0 Single Needle 2. Preparation and storage of liquid medicine Test substance - Nepicastat liquid medicine: Taking the preparation of 5 mg / mL nepicastat liquid medicine as an example: Weigh 50 mg of nepicastat into a brown sample bottle, add 1.98 mL of PEG400, vortex on a vortex mixer, sonicate for 15 minutes, heat in a water bath at 40 °C for 15 minutes to form a suspension, then add 0.99 mL of 30% Solutol HS15, vortex 2.97 mL of the suspension, and then add 6.93 mL of normal saline, vortex completely until a solution is formed. Prepare and use it freshly every day. Reference substance - Dexamethasone liquid medicine: Disperse dexamethasone in normal saline at a concentration of 0.1 mg / mL. Prepare and use it freshly every day. Reference substance - Tanshinone IIa liquid medicine: Dissolve tanshinone IIa in PBS containing 2% DMSO at a concentration of 0.0736 mg / mL. 3. Test method The test mice were female C57 mice purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., weighing 20 to 22 g, and were free of specific pathogens at the start of the experiment. (1) Modeling steps 1) Anesthetize C57 female mice (6 to 8 weeks old) by intraperitoneal injection of 5% chloral hydrate (70 μL / 10 g). 2) Clip the hair on the top of the head to expose the scalp, fix the mouse's head on the stereotaxic instrument for brain, and keep the top skull of the mouse roughly horizontal. Disinfect with iodophor. 3) Longitudinally cut the scalp about 0.5 cm, and find the anterior fontanelle and posterior fontanelle areas. Rotate the caliper of the stereotaxic instrument, move the tip of the microsyringe to the anterior fontanelle and posterior fontanelle areas, and keep the mouse's skull horizontal by observing the height of the tip from the anterior and posterior fontanelle points. After adjusting to the horizontal position, move the tip to the anterior fontanelle point, and then move it 2 mm to the right for positioning. 4) Mark the surface of the mouse's skull after positioning, and drill a hole at this point with a skull drill. During the drilling process, pay attention to avoiding blood vessels, drill carefully, and avoid damaging the dura mater and brain tissue. 5) Vertically insert a microsyringe into the mouse brain tissue using a stereotaxic apparatus. The vertical insertion depth is 3 mm. Keep the needle in place and wait for 5 min. 6) Turn on the infusion pump, select the Infuse Only mode, and set the speed to 1 μL / min for injection (2 μL of NMO-IgG + 3 μL of human complement + 5 μL of PBS / drug, premixed and homogenized by blowing, placed on ice). 7) After the injection is completed, wait for 10 min. Slowly pull out the needle upward by rotating the caliper. Stop the needle for 5 min after pulling it up 1 mm until the entire syringe needle is removed. Suture the skin and disinfect it again with iodophor. (2) Drug administration protocol Start drug administration 3 days before modeling and continue for 7 days after modeling, for a total of 10 consecutive days. The specific drug administration protocol is shown in Table 25 below. Table 25. Drug administration protocol (3) Sample collection On the 8th day of the model (i.e., the day after the last drug administration), euthanize the experimental mice and take brain tissues for frozen sections. Then measure the immunoreactive area of astrocyte markers in each group of mice and evaluate (for the experimental method, see the literature: Ye Gong et al., Journal of Neuroinflammation, 17(1). doi:10.1186 / s12974-020-01874-6). 4. Test results Figures 20A to 20D show that, from the perspective of the lesion ratios of AQP4 and GFAP, compared with the control group, the nepicastat group can significantly reduce the lesion ratio, and the effect is lower than that of the positive drug group. However, it has no significant effect on the immune parameters CD45 and IBA1. Therefore, nepicastat has a certain inhibitory effect on NMO-IgG-induced neuromyelitis optica in mice. Example 8: Therapeutic effect of a DBH inhibitor on imiquimod (IMQ)-induced psoriasis 1. Materials and equipment Table 26. Reagents Reagent Supplier Catalog number 5% Imiquimod cream Aldara, 3M Pharmaceuticals / Dexamethasone cream Sanjun Pharmaceutical Co., Ltd. H44024170 Tofacitinib citrate Dalian Meilun Biotechnology Co., Ltd. MB3358 PEG400 Sigma 202398 Solutol HS15 Sigma 42966 EtOH Shanghai Aladdin Biochemical Technology Co., Ltd. A500737-0500 Cremophor EL Sigma C5135 Poloxamer 188 Sigma 9003-11-6 Table 27. Equipment Equipment Model Electronic balance MFC: 9092250 Analytical balance SECURA225D-1CN+YDP20-0CEV1 Centrifuge Eppendorf_5424 Table 28. Test Animals Animal species and strain: Balb / c mice Breeder / supplier: Beijing Vital River Laboratory Animal Technology Co., Ltd. Gender, age: Female, 7-8 weeks Experimental institution: Wuxi Apptec Medical Technology Co., Ltd. (Nantong) Adaptation period: 7 days Room: SPF level Room temperature: 20-26°C Relative humidity: 40-70% Light cycle: 12 / 12 hours light / dark alternation Breeding density: 5 animals / cage Food and water: Free access to food and water All experiments conducted in this protocol have been approved by the Institutional Animal Care and Use Committee (IACUC) of Wuxi Apptec 2. Preparation and storage of drug solutions Test substance - Nepicastat oral administration solution: Prepare 9.9 mL of a 5 mg / mL nepicastat solution for oral administration: Weigh 50 mg of nepicastat, add 1.98 mL of PEG400, sonicate for 15 minutes, heat in a 40°C water bath for 15 minutes, and vortex to obtain a suspension. Add 0.99 mL of 30% Solutol HS15 to the 1.98 mL nepicastat suspension and vortex to obtain a suspension. Add 6.93 mL of normal saline to the 2.97 mL nepicastat suspension and vortex to obtain a solution Test substance - Nepicastat topical administration solution: Prepare 1 mL of nepicastat (50 mg / mL) for topical use: Weigh 50.13 mg of nepicastat, add 100 μL of PG, stir at 45°C for 10 minutes to obtain a homogeneous opaque suspension; then add 200 μL of ethanol and stir at 45°C for 5 minutes to obtain a homogeneous opaque suspension; then add 200 μL of Cremophor EL and stir at 45°C for 5 minutes to obtain a homogeneous opaque suspension. Then add 500 μL of 5% Poloxamer 188 to the suspension and stir at 45°C for 30 minutes to obtain a clear solution Reference substance - Tofacitinib citrate solution: Dissolve tofacitinib citrate in dimethyl sulfoxide to obtain a 5 mg / mL solution, and add 50 μL of the above solution to IMQ ointment for topical application 3. Test methods (1) Shave hair One day before the start of the experiment, the backs of all mice were shaved with a pet hair clipper, with an area of 2×3 cm (2) Grouping Sixty-five animals were randomly grouped by body weight, and the dosing regimens were as follows. Table 29. Grouping and dosing regimens Solvent A: 20% PEG400 + 10% (30% Solutol HS15) + 70% normal saline; Solvent B: 10% PG / 20% EtOH / 20% Cremophor EL / 50% (5% Poloxamer 188 aqueous solution). (3) Imiquimod and positive control preparations Imiquimod (IMQ) cream: From G2 to G7, the corresponding dose for each mouse was 62.5 mg of IMQ cream; Dexamethasone (DEX) ointment: The corresponding dose for each mouse in G4 was 70 mg of ointment; Tofacitinib: Tofacitinib was dissolved in dimethyl sulfoxide to 5 mg / mL, and 50 μL was added to the IMQ cream for daily treatment. (4) IMQ sensitization and dosing From day 0 to day 7, the mice in groups 2 to 7 received a daily topical dose of 62.5 mg of IMQ cream on the shaved back. The dosing of the test compounds and controls was carried out according to Table 29 for 7 consecutive days. (5) Disease assessment To evaluate the severity of the back skin inflammation, the back skin was scored according to Table 30. Erythema, scaling, and thickening were scored independently on a scale of 0 to 3, where 0 = none; 1 = mild; 2 = moderate; 3 = marked / severe. Table 30. Clinical scoring parameters (6) Experiment termination and sampling At the end of the experiment, the mice were euthanized by CO2 inhalation: 1) Blood was collected by cardiac puncture, and the plasma was processed, three portions in total, one portion in a protective solution and two portions were quickly frozen; 2) Five back skin samples from each group were placed in a protective solution; five back skin samples were placed in PFA; five back skin samples were quickly frozen; 3) Lymph nodes were collected and quickly frozen; 4) Spleen samples were collected and weighed (Figure 23). (7) Data statistics The data were statistically analyzed by one-way analysis of variance using Graph Pad Prism 6.0 software. 4. Research results (1) Body weight Throughout the study, body weight was monitored daily. Continuous use of the IMQ cream reduced the average body weight of the vehicle group. In addition, the body weight loss in the dexamethasone treatment group (G4) was more obvious. However, there was no statistically significant difference between the treatment group and the vehicle group (Figure 21). (2) Clinical score The erythema, scale, and thickness of the back skin were scored daily. In addition, the sum of the three (erythema + thickness + scale) was expressed as the total score. The dexamethasone treatment group had a significant inhibitory effect on inflammation, indicating that the psoriasis model induced by the IMQ cream was successful. The oral group of nepicastat inhibited erythema and thickness from day 5 to day 7. The topical group of nepicastat inhibited erythema from day 4 to day 7. Tofacitinib showed efficacy after the dose was doubled. Nepicastat treatment did not affect the disease development and incidence, but showed efficacy in the late stage of the disease course (day 5 to day 7). According to the total clinical score curves of the animals in each group, the area under the curve (AUC) was calculated (Figure 22). The inhibition rate was calculated according to the following formula: Inhibition rate = [AUC(vehicle) - AUC(treatment)] / AUC(vehicle) × 100%. Where: the vehicle refers to the vehicle group corresponding to the administration method. The inhibition rate of the dexamethasone treatment group was 96.96%. The 50mpk group of nepicastat treated orally had a significant inhibitory effect on the skin clinical score, and the inhibition rate was 23.64%. However, the 100mpk group of nepicastat treated topically had no obvious efficacy. Table 31. Results of erythema score Table 32. Results of scale score Table 33. Results of thickness score Table 34. Results of total score of erythema + scale + thickness 5. The purpose of this example was to study the efficacy of the test compound on the psoriasis model induced by IMQ. The results showed that the application of IMQ led to severe skin inflammation. Compared with the vehicle group control, the PO treatment group of nepicastat had a slight therapeutic effect on the clinical symptoms. Example 9: Therapeutic effect of DBH inhibitor on collagen-induced arthritis (CIA) in mice 1. Experimental materials Bovine type II collagen, CII, Sichuan University; Acetic acid, Sigma (St. Louis, MO, USA), Catalog No.: A8976; Complete Freund's adjuvant, Sigma, Catalog No.: F5881; 20% PEG400 + 10% (30% Solutol HS15) + 70% normal saline; Tofacitinib, >98%, Dalian Meilun Biotechnology Co., Ltd., MB3358. 2. Test compounds Table 35 Weigh 40 mg of the test substance into a brown sample vial, add 0.8 ml of PEG400, vortex on a vortex mixer, sonicate for 15 minutes, heat in a water bath at 40 °C for 15 minutes to form a suspension; then add 0.4 ml of 30% Solutol HS15 and vortex on a vortex mixer to mix evenly; then add 2.8 ml of normal saline and vortex on a vortex mixer to mix evenly until a solution is formed; the compound concentration is 10 mg / ml. Prepare it once every three days and store it at 4 °C for later use. 3. Experimental instruments Anesthesia machine: Raymain, RM-HSIV-u; High-speed homogenizer: IKA, T10basic; Compound weighing balance: Sartorius, CPA225D; Animal weighing balance: Changzhou Tianzhiping Electronic Balance, YH2000. 4. Experimental animals and breeding environment Animal strain: DBA / 1 mice Supplier: Beijing Vital River Laboratory Animal Technology Co., Ltd. Gender and body weight: Male, 14 - 20 g, specific pathogen free (SPF) Adaptation period: 3 - 7 days Environment: SPF animal breeding room, Wuxi AppTec Shanghai Waigaoqiao Animal Breeding Center Temperature: 20 - 26 °C Humidity: 40 - 70% Lighting: Fluorescent lamp, light (08:00 - 20:00), dark (20:00 - 08:00) for 12 hours each Breeding density: 5 animals / cage Food: Free access to food (irradiated sterilized feed) Drinking water: Free access to drinking water (prepared by Moore (ultra) pure water machine). The animal operations described in this example report have passed the review and approval of the Institutional Animal Care and Use Committee (IACUC) of Wuxi AppTec. 5. Experimental Methods 1) Immunization with Type II Collagen / Complete Freund's Adjuvant Preparation of acetic acid: Dilute 2N acetic acid to 100 mM, filter it with a 0.22-μm filter membrane, and store it at 4°C. Bovine Type II Collagen Solution: Dissolve bovine Type II collagen (CII) in 100 mM acetic acid solution and store it at 4°C overnight. The final concentration of collagen is 8 mg / mL. Preparation of emulsion: Mix the CII solution stored overnight with an equal volume of complete Freund's adjuvant, and use a high-speed homogenizer to homogenize it on ice at 30,000 revolutions per minute for about 60 minutes until a stable emulsion is formed. 2) Induction of Arthritis After anesthetizing DBA / 1 mice with isoflurane, inject 50 μL of the prepared collagen emulsion (containing 200 μg CII) subcutaneously at the tail. The first immunization day is recorded as day 0, and the subsequent days are marked sequentially. On day 21, inject the same volume of collagen emulsion at the tail. 3) Drug Administration and Dose Design When the model mice show clinical symptoms with an average score of about 0.5 (around day 28), re-randomly group them into 5 experimental groups of 8 mice each according to body weight and score. Administer the drug continuously for 14 days. The compound is prepared every 3 days and stored at 4°C. Table 36. Grouping and Dose Design 4) Determination of Arthritis Onset Index From after day 28, weigh the mice three times a week and record the clinical score until the end of the experiment. Clinical score: Score according to the degree of lesions (swelling and redness, joint deformation) according to the standard of 0 - 4 points. The maximum score for each limb is 4 points, and the maximum score for each animal is 16 points. Table 37. Clinical Scoring Criteria for Arthritis 5) Determination of Arthritis Onset Index a. Collect the hind paws of the mice, fix them in PFA for H&E staining and pathological scoring; b. Collect the spleens of the mice for FACS staining. 6) Statistical Analysis The experimental data are expressed as mean ± standard error. The body weight and clinical score are analyzed by two-way ANOVA. A p value < 0.05 is considered to indicate a significant difference. 6. Experimental Results Refer to Figures 24 to 27. Nepicastat has a certain known effect on collagen-induced arthritis in mice, but it is not as obvious as the positive control drug. Example 10: Therapeutic effect of DBH inhibitor on 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis in rats 1. Materials and equipment Table 38. Reagents Table 39. Instruments Instrument Supplier Model Enema hose France Vygon ACL 7157348 2. Preparation and storage of medicinal solutions Test substance - Nepicastat medicinal solution: Weigh 12 mg of nepicastat into a brown sample bottle, add 0.8 mL of polyethylene glycol 400, vortex and sonicate for 15 minutes, heat in a water bath at 40 °C for 15 minutes to form a suspension, then add 0.4 mL of 30% polyethylene glycol-15-hydroxystearate, vortex, and then add 2.8 mL of normal saline and vortex to completely dissolve it. Reference substance - Prednisone medicinal solution: The use concentration of prednisone is 0.9 mg / mL, and it is prepared into a suspension using 0.5% carboxymethylcellulose sodium, prepared twice a week. Preparation of DNBS medicinal solution: Dissolve DNBS powder in 30% ethanol to a final concentration of 50 mg / mL. 3. Treatment of rats Animal species and strain: Wistar rats; Medication record: No medication history; Gender, age, weight: Male, 5 to 6 weeks old, 160 to 180 g; Breeding party / supplier: Shanghai Slack Experimental Animal Co., Ltd.; Experimental institution: Animal house of PPL Biotech; Adaptation period: 7 days; Room: Ordinary area room; Indoor temperature: 20 to 26 °C; Indoor relative humidity: 40 to 70%; Lighting: Fluorescent lighting, 12 hours of lighting and 12 hours of no lighting; Animal feeding: 2 to 4 rats per cage (in the same dosing group); Food: Free access to feed (irradiated and disinfected, Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd., China); Water: Free access to drinking water (treated by reverse osmosis or autoclaved). A total of 90 male Wistar rats were purchased from Shanghai Slack Experimental Animal Co., Ltd. None of the animals carried specific pathogens and they were about 4 to 5 weeks old (140 to 150 g) when they arrived at the animal house of PPL Biotech. After the animals arrive at Pharmaron, the animal house staff will transfer the animals from the transport packaging to the cages and examine each animal. The examination scope includes appearance, limbs, orifices, etc., as well as whether there are abnormal manifestations when the animals are stationary or moving. The adaptation period is 7 days. The experimental operation plan designed for animals is approved by the Pharmaron IACUC (Institutional Animal Care and Use Committee). On day -1 (i.e., one day before the formal experiment), 90 animals are randomly grouped according to their body weights to ensure that the body weight values of each group of animals are similar and reduce deviation. The rats are fasted for 40 hours before the experiment, and during the fasting period, 5% glucose saline (10 mL / kg, once a day) is injected subcutaneously into the rats. Experimental grouping: On the first day of the experiment, the fasted rats are anesthetized by intraperitoneal injection of Zoletil (25 mg / kg tiletamine and 25 mg / kg zolazepam) and 5 mg / kg xylazine. For groups G2 - G6, a hose is inserted into the left colic flexure (about 8 cm from the anus) through the anus, and the rats are induced with colitis by enema with DNBS (0.5 mL / rat). The normal control group (G1) is given an enema with 30% ethanol in the same way. The animals given enema are placed with their heads down for 15 minutes, and then maintained in the Trendelenburg position until they wake up to avoid the backflow of the enema fluid. Table 40. Grouping and dosing regimen 4. Detection indicators (1) Animal body weight: The body weight of the animals is measured and recorded every day, and the daily activities of the animals are observed and abnormal situations are recorded. The body weight percentage is calculated according to the following formula: [(body weight on day x - initial body weight) / initial body weight]×100%. (2) Fecal score: During the experiment, the fecal status of the rats is scored every day (0 = normal, 1 = wet / sticky, 2 = soft, 3 = liquid). (3) Colon observation: After the experiment, all animals are anesthetized with Zoletil (intravenous injection, 25 mg / kg), the abdominal cavity is opened, blood is collected from the abdominal aorta, anticoagulated with EDTA (centrifugation conditions: 4°C, 2000 g, 10 min). After the animals are sacrificed by bleeding, the colon (from the cecum to the anus) is removed, and the colon length is immediately measured. The colon is longitudinally opened, rinsed, and then the colon weight, ulcer area are recorded and photographed as a whole. The colon is divided into three parts, two parts are frozen in liquid nitrogen and stored at -80°C for MPO and cytokine detection. Another part of the colon is fixed with 10% neutral formalin. If the ulcer is irregular in shape, it can be considered as a rectangle, and then its measured length and width are used to evaluate the ulcer area. Ulcer area (cm 2 ) = ulcer length (cm) × ulcer width (cm). (4) Pathological analysis of colon tissue The proximal, ulcerated (if no ulcer, take the approximate site), and distal parts of the colon tissue fixed with neutral formalin were embedded in paraffin, sectioned (thickness 5 μm), and stained with H&E for histopathological scoring. Table 41 5. Statistical analysis Experimental data were expressed as mean ± standard error. The data were analyzed by Graphpad Prism using the corresponding statistical methods. A p < 0.05 was considered to indicate a significant difference. 6. Experimental results (1) Body weight and fecal score are shown in Figures 28 to 31. (2) Macroscopic evaluation of the colon on day 7 Table 42. Macroscopic evaluation of the colon on day 7 Table 43. Macroscopic evaluation of the colon on day 7 BW: Body weight; CL: Colon length; CW: Colon weight; a : IR1 (Inhibition rate 1) = {[CW / CL / BW (model group) - CW / CL / BW (test drug group)] / [CW / CL / BW (model group) - CW / CL / BW (normal group)]} × 100%; b : IR2 (Inhibition rate 2) = {[CW / BW (model group) - CW / BW (test drug group)] / [CW / BW (model) - CW / BW (normal group)]} × 100%; c : IR3 (Inhibition rate 3) = {[CW / CL (model group) - CW / CL (test drug group)] / [CW / CL (model group) - CW / CL (normal group)]} × 100%. (3) Pathological score Table 44. Pathological score 7. Conclusion Inflammatory colitis was induced in Wistar rats by intracolonic perfusion of DNBS. Colitis was manifested as a significant decrease in the body weight of the animals, a significant increase in the fecal formability score, a significant shortening of the colon length, a significant increase in the colon weight, the colon weight:colon length (i.e., CW / CL), the colon weight:body weight ratio (i.e., CW / BW), and the colon weight:colon length:body weight ratio (i.e., CW / CL / BW), a significant increase in the colon ulcer area, and a significant increase in the colon inflammatory cell infiltration score and tissue damage score. In this example, the positive control drug prednisone could significantly reduce the fecal formability score AUC, intestinal weight, CW / CL, CW / BW, CW / CL / BW, and the colon ulcer end inflammatory cell infiltration score of the model rats. The inhibition rates of CW / CL / BW, CW / BW, and CW / CL were 44.20%, 50.13%, and 46.51% respectively. The inhibition rates of test group 1# (3 mg / kg) on CW / CL / BW, CW / BW, and CW / CL were 32.98%, 40.24%, and 30.82% respectively. Test group 2# (nizpestat 10 mg / kg) could significantly reduce CW / CL, CW / CL / BW, and the total colon tissue damage score. The inhibition rates of CW / CL / BW, CW / BW, and CW / CL were 44.95%, 47.06%, and 43.80% respectively. The inhibition rates of test group 3# (30 mg / kg) on CW / CL / BW, CW / BW, and CW / CL were 27.12%, 39.85%, and 26.68% respectively. In summary, nizpestat has a certain preventive and therapeutic effect on DNBS-induced colitis in rats. Example 11: Inhibitory effect of DBH inhibitor on dextran sulfate sodium (DSS)-induced colitis 1. Experimental materials Table 45. Reagents Table 46. Test substances Experimental animals: Strain C57BL / 6 mice; Source: Zhejiang Vital River Laboratory Animal Technology Co., Ltd.; Gender: female. Main instrument: Electronic balance: Sartorius, QUINTIX35-1CN. 2. Experimental method 2.1 Preparation and storage of compounds Weigh an appropriate amount of cyclosporine A (CsA) powder and place it in a brown sample bottle. Then add appropriate proportions of 2% DMSO, 30% PEG300, 5% Tween 80, and 63% Saline in sequence, and dissolve it by shaking. Prepare it once a day. Weigh an appropriate amount of nepicastat into a brown sample vial, and successively add appropriate amounts of 20% PEG400, 10% (30% Solutol HS15), and 70% normal saline in a certain proportion, mix well, and dissolve by ultrasonic treatment. Prepare it every three days to maintain its stability. Weigh an appropriate amount of fusaric acid and place it in a brown sample vial, add an appropriate amount of normal saline, and dissolve by ultrasonic treatment. Prepare it once every seven days. Weigh an appropriate amount of disulfiram and place it in a brown sample vial, successively add appropriate amounts of 50% PEG300 and 50% normal saline in a certain proportion, and dissolve it into a suspension. It should be mixed well before administration. Prepare it once every seven days. Weigh an appropriate amount of fumaric acid and place it in a brown sample vial, add an appropriate amount of normal saline, and dissolve it by heating in a water bath. Prepare it once a day. Table 47. Administration volume and drug storage concentration 2.2 Animal feeding 70 female C57BL / 6 mice, 8 weeks old, about 20 g in weight, are raised in individually ventilated cages (IVC, 5 mice in each cage), with the temperature controlled at (20 ± 2) °C and a 12 / 12-hour light / dark cycle. Before the experiment, the mice need to be adaptively fed in a SPF-class animal room for three days. During this period, ensure sufficient water and food. 2.3 Grouping and dosing regimen The experimental mice are adaptively fed in a SPF-class animal room for three days and then randomly divided into 7 groups (8 model groups and 1 control group), with 10 mice in each group. The mice start dosing from day 0 and end on day 7. Table 48. Animal grouping and dosing regimen 2.5 Establishment of the model In this example, a mouse enteritis model is established by DSS induction: The mice in the model group drink an aqueous solution of 3.1% DSS (sodium dextran sulfate, molecular weight 36000 - 50000) from day 0 to day 7. The DSS aqueous solution is freshly prepared and replaced every day to prevent degradation. The mice in the normal control group drink normal water. The experimental period is 9 days. At the end of the experiment, the mice are euthanized and samples are collected. 2.5 Disease Activity Index (DAI) scoring DAI scoring is performed every day. The DAI score consists of three parts: body weight change, fecal characteristics, and blood in the stool (or occult blood) scoring. The specific scoring criteria are shown in Table 49. During the entire experimental process, the DAI scores of all mice are completed by the same person. Table 49. DAI scoring criteria Percentage of body weight loss, stool characteristics, fecal occult blood or overt blood 00 Normal, fecal occult blood negative 1 1 - 5%, soft stool, fecal occult blood weakly positive 2 6 - 10%, loose stool, fecal occult blood positive 3 11 - 20%, watery stool, small amount of blood 4 >20%, watery stool, large amount of blood 2.6 Collection of colon tissue At the experimental endpoint, the mice were euthanized, the colon of the mice was dissected, photographed, the length was measured, and the contents were removed and then weighed. 2.7 Statistical analysis Data are expressed as mean ± standard error and were analyzed by two-way analysis of variance (two-way ANOVA) for body weight changes and disease activity scores, and Dunnett’s test was used for inter-group comparison. The remaining data were analyzed by one-way analysis of variance (one-way ANOVA) and Dunnett’s test was used for inter-group comparison. All analyses were performed using GraphPad Prism software. *P<0.05, **P<0.01, ***P<0.005, ****P<0.0001 vs. vehicle group. 3. Experimental results and analysis During the experiment, the body weight data of each group of mice were collected and the corresponding DAI scores were calculated. The data were analyzed by two-way ANOVA. As shown in Figure 32, compared with the vehicle group, the positive controls CsA (50 mg / kg, QD) and nepicastat (50 mg / kg, QD) effectively alleviated the DSS-induced body weight loss in mice. Compared with the vehicle group, fusaric acid (100 mg / kg, bid) and disulfiram (100 mg / kg, qd) did not effectively alleviate the DSS-induced body weight loss in mice. Fumaric acid (100 mg / kg, qd) tended to alleviate the DSS-induced body weight loss in mice. As shown in Figure 33, the disease activity index (DAI) scores of the positive control CsA (50 mg / kg, QD) group and the nepicastat (50 mg / kg, QD) group were significantly lower than those of the vehicle group. During the administration period, compared with the vehicle group, the DAI of the fusaric acid (100 mg / kg, bid) group, the disulfiram (100 mg / kg, qd) group and the fumaric acid (100 mg / kg, qd) group showed a slight improvement, which was more obvious on the 4th and 5th days, but the effect was lower than that of nepicastat. Based on the comprehensive analysis of body weight changes and DAI scores, it can be seen that the positive controls CsA (50 mg / kg, QD) and nepicastat (50 mg / kg, QD) effectively alleviated the symptoms of weight loss, diarrhea, and bloody stools in mice caused by DSS-induced colitis. The fusaric acid (100 mg / kg, bid) group, disulfiram (100 mg / kg, qd), and fumaric acid (100 mg / kg, qd) could slightly improve the symptoms of diarrhea and bloody stools in mice caused by DSS-induced colitis, but failed to effectively alleviate the weight loss in mice caused by DSS-induced colitis. References 1. Rush RA, Geffen LB. Dopamine beta-hydroxylase in health and disease. Critical Reviews in Clinical Laboratory Sciences. 1980, 12(3): 241-77. 2. Glennon RA. Phenylisopropylamine stimulants: amphetamine-related agents. Principles of Medicinal Chemistry (7th ed.). Philadelphia, USA: Wolters Kluwer Health / Lippincott Williams&Wilkins. 2013, pp. 646–648. ISBN 9781609133450. 3. Taylor KB. Dopamine-beta-hydroxylase. Stereochemical course of the reaction. J. Biol. Chem. 1974, 249(2): 454-458. 4. Horwitz D, Alexander RW, Lovenberg W, Keiser HR. Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity. Circ. Res. 1973, 32(5): 594-599. 5. Mutschler J, Abbruzzese E, Witt SH, Dirican G, Nieratschker V, Frank J, et al. Functional polymorphism of the dopamine β-hydroxylase gene is associated with increased risk of disulfiram-induced adverse effects in alcohol-dependent patients. Journal of Clinical Psychopharmacology. 2012, 32(4):578 - 80. 6. Ella E, Sato N, Nishizawa D, Kageyama S, Yamada H, et al. Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese. Journal of Human Genetics. 2012, 57(6):385 - 90. 7. Bhaduri N, Sinha S, Chattopadhyay A, Gangopadhyay PK, Singh M, Mukhopadhyay KK. Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children. Indian Pediatrics. 2005, 42(2):123 - 9. 8. Cubells JF, Sun X, Li W, Bonsall RW, McGrath JA, Avramopoulos D, Elston RC. Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia. Human Genetics. 2011, 130(5):635 - 43. 9. Combarros O, Warden DR, Hammond N, Cortina-Borja M, Belbin O, Lehmann MG, et al. The dopamine β-hydroxylase-1021C / T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project. BMC Medical Genetics. 2010, 11(161): 162. 10. Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, et al. Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase. British Journal of Pharmacology. 1997, 121(8): 1803–9. 11. Beliaev A, Learmonth DA, Soares-da-Silva P. Synthesis and biological evaluation of novel, peripherally selective chromanylimidazolethione-based inhibitors of dopamine beta-hydroxylase. J Med Chem. 2006, 49(3): 1191-7. 12. Cvek B., Dvorak Z. Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals. Current Pharmaceutical Design. 2007, 13(30): 3155–67. 13. Hegde SS, Friday KF. Dopamine-beta-hydroxylase inhibition: a novel sympatho-modulatory approach for the treatment of congestive heart failure. Current Pharmaceutical Design. 1998, 4(6): 469–79. 14. De La Garza, R 2nd, Bubar MJ, Carbone CL, Moeller FG, Newton TF, et al. Evaluation of the dopamine β-hydroxylase (DBH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2015, 59: 40-8. 15. Nunes T, Rocha JF, Vaz-da-Silva M, Igreja B, Wright LC, et al. Safety, tolerability, and pharmacokinetics of etamicastat, a novel dopamine-β-hydroxylase inhibitor, in a rising multiple-dose study in young healthy subjects. Drugs in R&D. 2010, 10(4): 225-242. 16. Almeida L, Nunes T, Costa R, Rocha JF, Vaz-da-Silva M, Soares-da-Silva P. Etamicastat, a novel dopamineβ-hydroxylase inhibitor: tolerability, pharmacokinetics, and pharmacodynamics in patients with hypertension. ClinTher. 2013, 35(12): 1983-96. 17. R. C. Alaniz, S. A. Thomas, M. 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Claims

1. Use of a pathway regulator in the preparation of a medicament for treating autoimmune diseases; wherein, The pathway regulator is one or more of a dopamine β-hydroxylase inhibitor, a receptor agonist, and a receptor antagonist.

2. The use according to claim 1, wherein, The pathway regulator is a dopamine β-hydroxylase inhibitor, and the dopamine β-hydroxylase inhibitor is one or more of nepicastat, etamicastat, imicastat, fusaric acid, disulfiram, cysteamine, pantethine, a copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts, and its prodrugs; Preferably, the dopamine β-hydroxylase inhibitor is selected from: nepicastat, etamicastat, imicastat, fusaric acid, disulfiram, fumaric acid, its pharmaceutically acceptable salts, and its prodrugs.

3. The use according to claim 1, wherein, The pathway regulator is nepicastat or its pharmaceutically acceptable salt, and the unit dose is: 10-100 mg / kg, preferably 20-50 mg / kg; or, The pathway regulator is etamicastat or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg, preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is imicastat or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg, preferably 90-110 mg / kg, more preferably 100 mg / kg; or The pathway regulator is fusaric acid or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg, preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is disulfiram or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg, preferably 90-110 mg / kg, more preferably 100 mg / kg; or, The pathway regulator is fumaric acid or its pharmaceutically acceptable salt, and the unit dose is 80-120 mg / kg, preferably 90-110 mg / kg, more preferably 100 mg / kg.

4. The use according to any one of claims 1-3, wherein, The autoimmune diseases are selected from: achalasia, Addison's disease, adult Still's disease, gammopathy, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM / anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune autonomic neuropathy, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease, autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, axonal neuropathy, Barlow's disease, Behçet's disease, benign mucous membrane pemphigoid, bullous pemphigoid, Castleman's disease, gluten allergy, Chagas disease, chronic inflammatory demyelinating polyneuropathy, chronic recurrent multifocal osteomyelitis, eosinophilic granuloma, cicatricial pemphigoid, Cogan syndrome, coldAgglutination disease, congenital heart block, Coxsackie myocarditis, acrosclerosis syndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis, neuromyelitis optica, discoid lupus, Dejerine syndrome, endometriosis, eosinophilic esophagitis, eosinophilic fasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis, giant cell myocarditis, glomerulonephritis, Goodpasture syndrome, granulomatosis with polyangiitis, hyperthyroidism, Guillain-Barré syndrome, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schönlein purpura, herpes gestationis or pemphigoid gestationis, hidradenitis suppurativa, hypogammaglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, immune thrombocytopenic purpura, inclusion body myositis, interstitial cystitis, juvenile arthritis, juvenile type I diabetes, juvenile myositis, Kawasaki disease, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus et atrophicus, ligneous conjunctivitis, linear IgA disease, lupus erythematosus, chronic Lyme disease, Meniere's disease, microscopic polyangiitis, mixed connective tissue disease, Mooren's corneal ulcer, Moebius syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal lupus, neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism, Pandas, paraneoplastic cerebellar degeneration, paroxysmal nocturnal hemoglobinuria, Parsonage-Turner syndrome, pars planitis, Paschen-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia, POEMS syndrome, polyarteritis nodosa, type I polyglandular syndrome, type II polyglandular syndrome, type III polyglandular syndrome, polymyalgia rheumatica, polymyositis, post-myocardial infarction syndrome, post-pericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia, pyoderma gangrenosum, Raynaud's phenomenon, reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren's syndrome, sperm and testicular autoimmunity, Stiff-person syndrome, subacute bacterial endocarditis, Susac syndrome, sympathetic ophthalmia, Takayasu arteritis, temporal arteritis / giant cell arteritis, thrombocytopenic purpura, thyroid ophthalmopathy, painful ophthalmoplegia syndrome, transverse myelitis, type I diabetes, ulcerative colitis, undifferentiated connective tissue disease, uveitis, vasculitis, vitiligo and Vogt-Koyanagi-Harada disease; Preferably, it is selected from any one of the following: autoimmune colitis, neuromyelitis optica, rheumatoid arthritis, scleroderma, psoriasis, uveitis; The autoimmune colitis is selected from any one of the following: Crohn's disease, ulcerative colitis.

5. A method for treating autoimmune diseases, which comprises the steps of: Administering a therapeutically effective amount of a pathway regulator to a subject; wherein, The pathway regulator is one or more of a dopamine β-hydroxylase inhibitor, a receptor agonist, and a receptor antagonist.

6. The method according to claim 5, wherein, The pathway regulator is a dopamine β-hydroxylase inhibitor, and the dopamine β-hydroxylase inhibitor is one or more of nepicastat, etamicastat, imicastat, fusaric acid, disulfiram, cysteamine, pantethine, a copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts, and its prodrugs; Preferably, the dopamine β-hydroxylase inhibitor is selected from: nepicastat, etamicastat, imicastat, fusaric acid, disulfiram, fumaric acid, its pharmaceutically acceptable salts, and its prodrugs.

7. The method according to claim 5 or 6, wherein, The autoimmune disease is as defined in claim 4.

8. A pharmaceutical composition for treating autoimmune diseases, which comprises: A pathway regulator, and A pharmaceutically acceptable carrier; wherein, The pathway regulator is one or more of a dopamine β-hydroxylase inhibitor, a receptor agonist, and a receptor antagonist.

9. The pharmaceutical composition according to claim 8, wherein, The pathway regulator is a dopamine β-hydroxylase inhibitor, and the dopamine β-hydroxylase inhibitor is one or more of nialamide, etomidate, emetine, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs; Preferably, the dopamine β-hydroxylase inhibitor is selected from nialamide, etomidate, emetine, fusaric acid, disulfiram, fumaric acid, its pharmaceutically acceptable salts and its prodrugs.

10. The pharmaceutical composition according to claim 8, wherein, The autoimmune disease is as defined in claim 4.

11. The use according to claim 1, wherein the medicament is for one or more selected from the following: Reduce the proportion of CD4+ T cells, increase the proportion of regulatory T cells, increase the proportion of CD8+ T cells, reduce the secretion of pro-inflammatory factors by CD4+ T cells, reduce the secretion of pro-inflammatory factors by CD8+ T cells, inhibit the activation of B cells and inhibit the activation of NK cells; reduce the content of lymphocytes, neutrophils and monocytes in peripheral blood; reduce inflammatory cell infiltration in the dermis and capillary proliferation under the dermis; Improve skin fibrosis; reduce the incidence of uveitis; Improve skin inflammation; Improve fecal formability score, improve CW / CL, improve CW / BW, improve CW / CL / BW, inhibit the increase in colonic ulcer area, improve colonic inflammatory cell infiltration score, improve tissue damage score; improve disease activity score, improve blood in stool or occult blood.

12. The use according to claim 11, wherein: The pro-inflammatory factors of the CD4+ T cells are one or more of IL-17A, IFN-γ and TNF-α; The pro-inflammatory factors of the CD8+ T cells are IL-17A and / or TNF-α.

13. The use according to claim 11, wherein, The regulatory T cells are CD25+FOXP3+ Treg cells; And / or, the B cells are B220+ cells, preferably CD69+B220+ B cells; And / or, the NK cells are NK1.1+ cells, preferably NK1.1+CD107a+ NK cells.

14. A method for regulating the function of immune cells in vivo or in vitro, comprising the following steps: Contacting an effective amount of a pathway regulator with immune cells in vivo or in vitro, wherein, The immune cells are from a subject; The pathway regulator is one or more of a dopamine β-hydroxylase inhibitor, a receptor agonist and a receptor antagonist; The regulation of immune cell function refers to one or more functions selected from the following: reducing the proportion of CD4+ T cells, increasing the proportion of regulatory T cells, increasing the proportion of CD8+ T cells, reducing the secretion of pro-inflammatory factors by CD4+ T cells, reducing the secretion of pro-inflammatory factors by CD8+ T cells, inhibiting the activation of B cells and inhibiting the activation of NK cells.

15. The method according to claim 14, wherein, The dopamine β-hydroxylase inhibitor is one or more of nialamide, etomidate, emetine, fusaric acid, disulfiram, cysteamine, pantethine, copper chelator, fumaric acid, hydralazine, 2-thiophen-2-ylallylamine, its pharmaceutically acceptable salts and its prodrugs; Preferably, the dopamine β-hydroxylase inhibitor is selected from: nialamide, etomidate, emetine, fusaric acid, disulfiram, fumaric acid, its pharmaceutically acceptable salts and its prodrugs.

16. The method according to claim 14, wherein: The pro-inflammatory factors of the CD4+ T cells are one or more of IL-17A, IFN-γ and TNF-α; The pro-inflammatory factors of the CD8+ T cells are IL-17A and / or TNF-α.

17. The method according to claim 14, wherein, The regulatory T cells are CD25+FOXP3+ Treg cells; And / or, the B cells are B220+ cells, preferably CD69+B220+ B cells; And / or, the NK cells are NK1.1+ cells, preferably NK1.1+CD107a+ NK cells.