Application of compound in preparation of medicine for preventing or treating fibrosis diseases

Abstract

The invention belongs to the technical field of biological medicines, and discloses an application of a compound in preparation of a medicine for preventing or treating fibrosis diseases, and the fibrosis diseases comprise one of pulmonary fibrosis, renal fibrosis, hepatic fibrosis, myocardial fibrosis and skin fibrosis. New application of the compound NCG, namely application of the compound NCG in preparation of the medicine for preventing or treating fibrosis diseases, is found for the first time, and the compound NCG has good clinical application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of a compound in the preparation of a drug for preventing or treating fibrotic diseases. Background Art

[0002] Fibrosis is defined as the excessive proliferation of fibroblasts in an organ, accompanied by the aggregation of a large amount of deposited extracellular matrix, which destroys the tissue structure. In the late stages of the course of various diseases, such as viral hepatitis, chronic nephritis, scleroderma, coronary heart disease, etc., fibrosis will occur in the organs and ultimately lead to organ failure. Common fibrotic diseases include pulmonary fibrosis, renal fibrosis, liver fibrosis, myocardial fibrosis, and skin fibrosis. Pulmonary fibrosis is considered an age-related disease. With the increasing aging of the population, the incidence and mortality of pulmonary fibrosis have been increasing year by year (Cho, S.J. and H.W. Stout-Delgado, Annual Review of Physiology, 2020. 82: p. 433-459.). A large number of studies have shown that a large number of alveolar type II epithelial cells rich in Tp53, TGFβ1, DNA damage response signals, and senescence markers accumulate in fibrotic lung tissues, emphasizing the important role of alveolar epithelial cell senescence in the occurrence and development of pulmonary fibrosis (Kobayashi, Y., et al., Nature Cell Biology, 2020. 22(8): p. 934-946.). Targeting senescent cells and inhibiting the senescence-associated secretory phenotype (SASP) are potential treatment strategies against pulmonary fibrosis, however, its exact mechanism and targeted treatment methods have not been elucidated yet.

[0003] Currently, the treatment methods for fibrotic diseases mainly include drug treatment and organ transplantation. As the only ultimate treatment option for patients with fibrotic diseases, the application and popularization of organ transplantation are limited by difficulties in obtaining donors, high surgical risks, and high surgical costs. Existing drugs cannot reverse the fibrotic course, and their clinical treatment effects and safety cannot meet the treatment requirements. Therefore, it is urgent to deeply study the occurrence mechanism of fibrotic diseases, find new treatment targets, fully combine with the innovative pharmaceutical development trend, and develop new drugs that can effectively treat fibrotic diseases and have high safety. Summary of the Invention

[0004] Aiming at the problems existing in the prior art, the purpose of the present invention is to provide the application of a compound in the preparation of a drug for preventing or treating fibrotic diseases, which has good clinical application value.

[0005] To achieve the above purpose, the present application adopts the following technical solutions: In the first aspect, the present invention provides the application of a compound in the preparation of a drug for preventing or treating fibrotic diseases, and the structural formula of the compound is:

[0006] In the above technical solution, the compound exerts the ability to prevent or treat fibrotic diseases by reducing the transcriptional levels and protein expression levels of fibronectin, type I collagen, and α-SMA.

[0007] In the above technical solution, the compound exerts the ability to prevent or treat fibrotic diseases by reducing the expression levels of senescence markers p16, p21, and p53.

[0008] In the above technical solution, the fibrotic disease includes one of pulmonary fibrosis, renal fibrosis, hepatic fibrosis, myocardial fibrosis, and skin fibrosis.

[0009] In the above technical solution, the fibrotic disease is pulmonary fibrosis, and the compound slows down the process of pulmonary fibrosis by inhibiting the senescence of type II alveolar epithelial cells.

[0010] In a second aspect, the present invention provides the use of a drug in the preparation of a drug for preventing or treating fibrotic diseases. The drug consists of a compound at an effective dose, which can be a single component or a composition containing the compound at an effective dose. The composition may include pharmaceutically acceptable excipients. The structural formula of the compound is:

[0011] In the above technical solution, the drug is a drug for preventing or treating fibrotic diseases. The compound reduces the transcriptional levels and protein expression levels of fibronectin, type I collagen, and α-SMA, so that the drug exerts the ability to prevent or treat fibrotic diseases.

[0012] In the above technical solution, the drug is a drug for preventing or treating fibrotic diseases. The compound reduces the expression levels of senescence markers p16, p21, and p53, so that the drug exerts the ability to prevent or treat fibrotic diseases.

[0013] In the above technical solution, the dosage form of the drug is injection, tablet, powder for injection, granule, capsule, oral liquid, ointment, or cream.

[0014] In the above technical solution, the excipients are one or more of diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners, and fragrances.

[0015] The beneficial effect of the present invention is that the present invention discovers for the first time a new application of the compound NCG, that is, the application of the compound NCG in the preparation of a drug for preventing or treating fibrotic diseases, which has good clinical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 These are the Masson staining result diagrams of the lung tissues of three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG; Figure 2 These are the schematic diagrams of the Ashcroft scores of fibrosis in the three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG. Among them, **p < 0.01, ****p < 0.0001; Figure 3 These are the schematic diagrams of the western blot results of fibronectin and type I collagen in the lung tissues of three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG. Among them, *p < 0.05; **p < 0.01, ***p < 0.001, and Figure 3 a is the diagram showing the test results, Figure 3 b is Figure 3 the bar chart of a; Figure 4 These are the schematic diagrams of the quantitative RT-PCR results of fibronectin, type I collagen, and α-SMA in the lung tissues of three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG. Among them, ***p < 0.001, ****p < 0.0001; Figure 5 These are the schematic diagrams of the lung function results in the three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG. Among them, *p < 0.05, **p < 0.01, ***p < 0.001; Figure 6 These are the schematic diagrams of the western blot results of the senescence markers p16, p21, and p53 in A549 cells intervened with bleomycin after pretreatment with normal saline and NCG respectively. Among them, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; Among them, Figure 6 a is the diagram showing the test results, Figure 6 b is Figure 3 the bar chart of a; Figure 7 These are the schematic diagrams of the western blot results of the senescence markers p16, p21, and p53 in the lung tissues of three groups of mice intervened with normal saline, bleomycin, and bleomycin + NCG. Among them, **p < 0.01, ***p < 0.001, ****p < 0.0001; Among them, Figure 7 a is the diagram showing the test results, Figure 7 b is Figure 3 the bar chart of a. Specific implementation manners

[0017] To better illustrate the objectives, technical solutions, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. The present invention can be implemented in many different forms and should not be construed as limited to the embodiments set forth herein. On the contrary, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the present invention to those skilled in the art. The present invention will be defined only by the claims.

[0018] Definition and Use of Terms Fibrotic diseases: In the present invention, fibrotic diseases include pulmonary fibrosis, renal fibrosis, myocardial fibrosis, liver fibrosis, and skin fibrosis. Among them, liver fibrosis refers to the pathological process of abnormal proliferation of connective tissue in the liver caused by various pathogenic factors and excessive precipitation of extracellular matrix diffusely in the liver. A variety of factors can cause liver fibrosis, such as viral infection, inflammatory reaction, oxidative stress, and alcoholism. The pathological characteristics of liver fibrosis are a large amount of fibrous tissue hyperplasia and deposition in the portal area and hepatic lobules, but no intralobular septum has been formed yet. In cirrhosis, there are pseudolobules formed, and there are septa in the central vein area and portal area, and the normal structure of the liver is damaged. The further development of liver fibrosis is cirrhosis. Chronic liver diseases in China are mainly viral hepatitis. The liver tissue fibrosis caused by chronic viral hepatitis is related to liver inflammation, necrosis, virus replication, etc. This disease course is reversible in the early stage. Therefore, by organically combining treatment regimens such as antiviral and regulating the body's immune function, the process of liver fibrosis can be controlled to a certain extent.

[0019] The main pathological characteristics of pulmonary fibrosis include proliferation of mesenchymal cells in the lung tissue, hyperplasia and deposition of extracellular matrix, and remodeling of the lung parenchyma, etc. Currently, measures such as anti-inflammatory, antioxidant, anti-fibroblast proliferation and collagen deposition, and lung transplantation are mainly used to treat pulmonary fibrosis.

[0020] Renal fibrosis is a pathological process in which a large amount of extracellular matrix and connective tissue accumulate in the kidney, leading to changes in the kidney structure and impaired function. Almost all kidney diseases progress to the end stage with the occurrence of renal fibrosis and ultimately lead to kidney failure. The process of renal fibrosis involves inflammatory reactions, apoptosis of renal tubular epithelial cells, and imbalance of various fibrotic regulatory cytokines, etc. Therefore, renal fibrosis can be prevented and treated through anti-inflammatory, anti-apoptosis, and treatment targeting fibrotic cytokines and other approaches.

[0021] Myocardial fibrosis is mainly characterized by the proliferation of fibroblasts and the deposition of extracellular matrix in the normal tissue structure of the myocardium. Currently, it is considered to be mainly caused by hypertensive heart disease, ischemic cardiomyopathy, dilated cardiomyopathy, viral myocarditis, diabetic cardiomyopathy, etc. Myocardial fibrosis causes an increase in the hardness of the heart and a decrease in compliance, affecting the normal diastolic and systolic functions of the heart, and is a key factor in the prognosis of cardiovascular diseases.

[0022] Skin fibrosis forms scar tissue. Scar tissue is the fibrous connective tissue in the aging stage formed by the remodeling and maturation of granulation tissue. In cases such as trauma, fibroblasts divide, proliferate, migrate to the damaged site, produce extracellular matrix, form scar tissue, and repair the trauma.

[0023] Individual: In the present invention, the term "individual" refers to mammals, including but not limited to rats, mice, non-human primates, humans, dogs, cats, horses, cows, sheep, pigs, goats. Preferably, it is a human or a mouse.

[0024] Prevention and treatment: As used in the present invention, "prevention" means preventing or reducing the occurrence of fibrosis after use in the presence of possible fibrogenic factors. "Treatment" as used in the present invention means reducing the degree of fibrosis, or curing fibrosis to make it normal, or slowing down the process of fibrosis.

[0025] The present invention has confirmed that the compound NCG can significantly reduce bleomycin-induced senescence of type II alveolar epithelial cells through the following examples. Among them, alveolar epithelial cell senescence plays an extremely important role in the pathogenesis of fibrotic diseases including liver fibrosis, pulmonary fibrosis, renal fibrosis, and skin fibrosis.

[0026] The present invention also discloses a pharmaceutical composition comprising the compound NCG, which comprises the above-mentioned compound NCG and pharmaceutically acceptable excipients. The pharmaceutical composition can be in the form of an injection, capsule, tablet, nasal spray, or aerosol, etc., and is administered to the subject individual in an acceptable manner for the individual, such as by injection, oral administration, nasal spraying, etc.

[0027] To better explain the present invention, the following is a detailed description in conjunction with specific examples.

[0028] Example 1 Effect of compound NCG on the degree of fibrosis Experimental animals and materials: 1. Experimental animals: Source, strain, and line: Wild-type mice (WT, C57BL / 6) purchased from Nanjing Genscript Biotech Co., Ltd.; Reproductive age: 8 - 10 weeks old.

[0029] 2. Experimental materials: Bleomycin: Purchased from Pfizer Pharmaceuticals Ltd.; Sodium pentobarbital: Shanghai Sixin Biotechnology Co., Ltd.; Normal saline: Shanghai Baxter Medical Supplies Co., Ltd.; Compound NCG: Purchased from MedChemExpress (MCE), USA.

[0030] 3. Experimental methods: Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (70 mg / kg), and then bleomycin with a final concentration of 2 U / kg was injected through the airway. The bleomycin was dissolved in 40 μL of physiological saline, and mice injected with the same volume of physiological saline through the airway were used as controls. NCG was instilled into the nasal cavity (20 mg / kg) starting on the 10th day after administration of bleomycin or physiological saline, and the mice were sacrificed on the 21st day.

[0031] Construction of a bleomycin-induced mouse pulmonary fibrosis model (1) Preparation of items The mouse pulmonary drug delivery device (airway drug delivery high-pressure needle, scissors, straight forceps, curved forceps) was autoclaved in advance, and other items such as a halogen lamp (taken to the animal room one day in advance and disinfected by the teacher), isoflurane, timer, empty tip box, sterile gauze, sterile disposable pads, alcohol cotton balls, 1 ml and 5 ml syringes, adhesive tape, sputum cup, spare PBS or physiological saline, experimental record forms, pens, etc. were disinfected by ultraviolet light and then entered the SPF-class animal room.

[0032] (2) Preparation of the operating table After wiping the table with alcohol and waiting for it to dry, place the cold light source, lay a sterile disposable pad, fix the mouse fixing plate and clean gauze with adhesive tape, reserve a relatively clean place to place the instruments with clean PE gloves (with sterile gauze on top), adjust the light source brightness of the halogen lamp to facilitate observing the mouse's throat, and adjust the appropriate seat height for modeling.

[0033] (3) Preparation for airway drug delivery Use adhesive tape to fix a mark in the middle of the suspension line of the mouse fixing plate to prevent the mouse from moving during the modeling process; mark the bottom of the airway drug delivery high-pressure needle with adhesive tape of appropriate length to facilitate controlling the injection depth; wrap both ends of the straight forceps with adhesive tape to prevent hurting the mouse when pulling the mouse's tongue; assemble the airway drug delivery high-pressure needle and tighten the connection between the needle head and the pillow core to avoid air leakage; pour sterile PBS into a sterile sputum cup, immerse the assembled airway drug delivery high-pressure needle head under the PBS liquid level, quickly push and pull the pillow core to expel the excess air in the needle; after expelling all the air, aspirate an appropriate amount of liquid, quickly push the pillow core under the light source to observe the atomization situation of the airway drug delivery high-pressure needle. If the atomization is fast and the mist is fine and uniform, subsequent tests can be carried out; aspirate an appropriate amount of drug (50 - 70 μl of liquid) with the airway drug delivery high-pressure needle before use.

[0034] (4) Mouse anesthesia Place a sterile cotton ball in a transparent empty tip box, aspirate 1 ml of isoflurane with a 5 ml syringe and evenly inject it onto the cotton ball, cover the lid, and after about 1 min, the isoflurane concentration in the box is appropriate. Put the mouse into the anesthesia box, closely observe the mouse's breathing. After about 30 - 50 s, when the mouse shows nodding-like breathing, the mouse can be taken out.

[0035] (5) Airway administration Hang the anesthetized mice on the mouse fixing plate, adjust the brightness and height of the halogen lamp to observe the airways of the mice; hold a curved forceps in the left hand and a straight forceps in the right hand. After moving the mouse's tongue out of the left corner of the mouse's mouth with the straight forceps, place it at a suitable position in the mouse's oral cavity with the curved forceps to support between the upper jaw and the tongue, avoiding the suffix of the root of the tongue, and try to expose the oral cavity for easy observation of the airway; when we see obvious glottis movement, replace the straight forceps in the right hand with a high-pressure needle for airway administration, accurately insert the needle tip of the high-pressure needle for airway administration into the appropriate position of the airway. At this time, it can be seen that the breathing frequency of the mouse slows down; at this time, slowly withdraw the curved forceps in the left hand from the mouse's oral cavity, replace the left hand with the right hand to hold the needle handle, quickly withdraw the pillow core with the right hand, keep the needle tip in the airway for about 10 s, take out the high-pressure needle for airway administration, and observe that the mouse's breathing significantly accelerates, and there is no obvious liquid overflow from the mouse's oral cavity and nose, indicating successful airway administration.

[0036] (6) Mouse care Remove the mouse from the mouse fixing plate, keep the mouse in a vertical position, shake the mouse left and right, and closely observe the basic vital signs of the mouse such as breathing, and put it back after the mouse is fully awake.

[0037] (7) Observation and record Within the next 21 days, observe the vital activities of the mice every 2 days, record the body weight of the mice every 7 days, clean up the dead mice in time and make records, and collect mouse specimens on the 21st day after modeling for subsequent detection.

[0038] (8) Precautions For the mice used for modeling, try to keep them above 25 g to avoid the mice being unable to withstand the BLM strike.

[0039] Pay attention to aseptic operation throughout the process to avoid subsequent mouse infection; pay attention to the anesthesia level of the mice throughout the process to avoid mouse death due to excessive anesthesia; operate gently throughout the process to avoid harming the mice.

[0040] Lung tissue pathological section and scoring method: After the left lung tissue is fixed with formaldehyde, dehydrated with ethanol, embedded in paraffin, and sectioned; after dewaxing the sections, perform Masson staining (masson) to analyze the degree of pulmonary fibrosis in each mouse. Two pathologists independently evaluate the severity of interstitial fibrosis in each continuous area in a blinded manner using the Ashcroft scoring system. The specific scoring rules are as follows: 4. Experimental results: Specifically, the results of Masson trichrome staining of the lung tissues of mice intervened with normal saline, bleomycin, and bleomycin + NCG are as Figure 1 shown, combined withFigure 1 It can be seen that after being stimulated and induced by bleomycin, the lung tissue of mice showed fibrotic changes, while NCG intervention significantly alleviated lung injury and fibrosis in mice.

[0041] The results of the Ashcroft score were as Figure 2 shown, and it can be seen from Figure 2 that bleomycin can significantly induce fibrotic changes in the lungs, manifested as a significant increase in the Ashcroft score compared with the normal saline group; while the Ashcroft score of the bleomycin + NCG intervention group of mice was lower than that of the bleomycin group, indicating that the degree of pulmonary fibrosis was greatly alleviated.

[0042] Example 2 Effects of compound NCG on the protein and mRNA levels of fibronectin, type I collagen and α-SMA To further evaluate the degree of fibrosis in each mouse after bleomycin injection, the present invention detected the protein and mRNA levels of fibronectin, type I collagen and α-SMA in the lung tissues of each group of mice by western blot and RT-PCR methods respectively.

[0043] Specifically, the lung tissues of the mice after the experiment in Example 1 were collected, the proteins in the tissues were extracted by RIPA lysis buffer, and the target proteins, such as the expression levels of fibronectin, type I collagen and α-SMA, were detected by Western blot. The results were as Figure 3 shown. Among them, Western blot was referenced from Wang et al., 2017, Journal of Allergy and Clinical Immunology 40: 1550 - 1561.

[0044] Meanwhile, SYBR Premix Ex Taq (TaKaRa) was used for fluorescence quantitative RT-PCR, and β-actin was used as an internal reference to normalize the relative expression of each target gene. The results were as Figure 4 shown. The primers corresponding to each target gene are listed in Table 1 below. Among them, the specific test expression method was as described in Chen et al., 2015, International journal of clinical and experimental pathology 8: 6700 - 6707.

[0045] Specific method: a. Reverse transcription (1) Prepare items TAKARA reverse transcription kit was used for mRNA reverse transcription. The reverse transcription kit was melted on ice; the mRNA sample was melted on ice; the tip box and EP tubes to be used were autoclaved at high temperature in advance; (2) Preparation System Calculate the amount of cDNA required subsequently, increase and prepare the reverse transcription volume proportionally according to the components in the following table, and add it to a 200 μl EP tube. Reagent Dosage (10ul system) 5×PrimeScript RT Master Mix 2 mRNA 2 (500ng) DEPC Water 6 (3) Reverse Transcription Gently mix the samples evenly, centrifuge them, and place them in a conventional PCR instrument. Set the following reverse transcription program: Steps Temperature Time 1 37℃ 15min 2 85℃ 5s 3 4℃ 5min (4) Sample Dilution and Preservation Dilute the samples appropriately according to the CT value of the internal reference. Generally, the lung tissue samples are diluted 5-fold and stored in a -80 °C refrigerator for a long time.

[0046] b. Fluorescent Quantitative PCR (1) Preparation (A) The TAKARA kit is used for RT-PCR and thawed on ice; (B) The cDNA samples are thawed on ice; (C) The primers are thawed on ice. All the primers required in this article are from mice. The specific primer information is shown in the following table: (2) Preparation of RT-PCR System Prepare according to the following system: Reagent Dosage (ul) 2×SYBR Premix Ex Taq 5.0 Primer Forword 0.2 Primer Reverse 0.2 DEPC Water 2.6 cDNA 2.0 (3) RT-PCR Detection Cover the PCR plate with a film, centrifuge for 2 min, and place it in an RT-PCR instrument to run the following program: (4) Data Analysis The data is normalized with β-Actin as the internal reference and transformed by 2-ΔΔCT relative to the normal value.

[0047] Combined with Figure 3 and Figure 4 It can be seen that compared with the normal saline group, the lung tissues of mice in the bleomycin group showed significant pulmonary fibrosis, manifested as an increase in the fibrosis indexes fibronectin, type I collagen, and α-SMA; compared with the bleomycin group, the transcriptional levels and protein expression levels of fibronectin, type I collagen, and α-SMA in the bleomycin + NCG intervention group of mice were decreased, indicating that NCG intervention can significantly reduce pulmonary fibrosis in mice.

[0048] Example 3 Effect of Compound NCG on Lung Function 1. Experimental Instruments: Mouse Pulmonary Function Tester: Shanghai Sirike Biotechnology Co., Ltd.

[0049] 2. Experimental Methods: (1) Instrument Preparation Assemble the mouse pulmonary function tester, connect it to the computer, check the airtightness of the device after opening the program, calibrate the instrument, and set the parameters for pulmonary function measurement.

[0050] (2) Mouse Preparation Weigh the mouse. After the mouse is anesthetized, check the depth of anesthesia. Then, intubate the mouse trachea according to the method mentioned above.

[0051] (3) Measure the Pulmonary Function of Mice Connect the mouse to the mouse pulmonary function tester. After inputting and verifying the basic information of each mouse in Example 1, observe the cooperation between the mouse's breathing and the mouse pulmonary function tester. When it is observed that the mouse shows no obvious resistance, start measuring the following relevant respiratory indexes: SnapShot-150, Quick Prime-3, Deep Inflation, PV-loops. Each index is measured at least three times. After the pulmonary function measurement of the mouse is completed, take the corresponding specimens of the mouse.

[0052] The measurement results are as Figure 5 shown. Combining Figure 5 it can be known that, consistent with the expression results in Example 2 above, compared with the mice in the bleomycin group, the indexes such as inspiratory volume, lung compliance, and lung elastic resistance of the mice in the bleomycin + NCG intervention group are significantly improved.

[0053] Example 4 Effects of Compound NCG on the Senescence of Type II Alveolar Epithelial Cells and Mouse Lung Tissue Through experiments, more and more evidence shows that the senescence of alveolar epithelial cells is crucial for the occurrence and development of pulmonary fibrosis. Therefore, the present invention further detected the effect of NCG on the senescence of alveolar epithelial cells stimulated by bleomycin.

[0054] As Figure 6 shown by the western blot results, the expressions of senescence markers p16, p21, and p53 in A549 cells stimulated with 10 μg / ml BLM using NCG were significantly decreased.

[0055] As Figure 7 shown by the western blot results, bleomycin significantly induced the senescence of mouse lung tissue, manifested as a significant increase in the expressions of senescence markers p16, p21, and p53; compared with the bleomycin group, the expressions of senescence markers p16, p21, and p53 in the lung tissue of mice in the bleomycin + NCG intervention group were significantly decreased.

[0056] In summary, the above experimental data indicate that the compound NCG can alleviate bleomycin-induced senescence of mouse lung tissue by inhibiting the senescence of type II alveolar epithelial cells, thereby slowing down the fibrosis process.

[0057] Therefore, the compound NCG studied in the present invention provides a new treatment strategy for fibrosis diseases that currently lack effective treatment methods.

[0058] Obviously, the above embodiments are merely examples for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. Use of a compound in the preparation of a drug for preventing or treating fibrotic diseases, characterized in that: The structural formula of the compound is:

2. The application according to claim 1, characterized in that: The compound exerts the ability to prevent or treat fibrotic diseases by reducing the transcription level and protein expression level of fibronectin, type I collagen and α-SMA.

3. The application according to claim 1, characterized in that: The compound exerts the ability to prevent or treat fibrotic diseases by reducing the expression levels of senescence markers p16, p21 and p53.

4. The application according to claim 1, characterized in that: The fibrotic disease includes one of pulmonary fibrosis, renal fibrosis, liver fibrosis, myocardial fibrosis and skin fibrosis.

5. The application according to claim 1, characterized in that: The fibrotic disease is pulmonary fibrosis, and the compound inhibits the senescence of type II alveolar epithelial cells, thereby slowing down the progress of pulmonary fibrosis.

6. Use of a drug in the preparation of a drug for preventing or treating fibrotic diseases, characterized in that: The drug is composed of a compound at an effective dose, which may be a single component or a composition containing an effective dose of the compound, wherein the composition may include pharmaceutically acceptable excipients, and the structural formula of the compound is:

7. The use according to claim 6, characterized in that: The drug is a drug for preventing or treating fibrotic diseases. The compound reduces the transcription level and protein expression level of fibronectin, type I collagen and α-SMA, so that the drug exerts the ability to prevent or treat fibrotic diseases.

8. The use according to claim 6, characterized in that: The drug is a drug for preventing or treating fibrotic diseases. The compound reduces the expression levels of senescence markers p16, p21 and p53, so that the drug has the ability to prevent or treat fibrotic diseases.

9. The use according to claim 6, characterized in that: The dosage form of the drug is injection, tablet, powder injection, granule, capsule, oral solution, ointment, or cream.

10. The use according to claim 6, characterized in that: The auxiliary material is one or more of a diluent, a lubricant, a wetting agent, an emulsifier, a suspension stabilizer, a preservative, a sweetener and a flavor.

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