Application of ME1 in preparation of medicine for preventing and / or treating inflammatory bowel disease

Abstract

The invention belongs to the technical field of biomedicine, and particularly relates to application of ME1 in preparation of a medicine for preventing and / or treating inflammatory bowel diseases. The invention discloses an application of an ME1 inhibitor in preparation of drugs for preventing and / or treating inflammatory bowel diseases, and an application of a substance for detecting ME1 in preparation of drugs for diagnosing or detecting inflammatory bowel diseases. The action effect of ME1 * in disease treatment is evaluated through a mouse IBD model induced by dextran sodium sulfate DSS and trinitrobenzene sulfonic acid TNBS, so that a new strategy and method are provided for clinical intervention of IBD. In addition, the invention also clarifies the application of the ME1 as a high-specificity biomarker in IBD diagnosis, and further expands the comprehensive value of the ME1 in disease prevention and treatment.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to the application of ME1 in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease. Background Technology

[0002] Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic gastrointestinal inflammation, primarily including Crohn's disease (CD) and ulcerative colitis (UC). Its typical clinical manifestations include recurrent abdominal pain, diarrhea, and weight loss, and it can be accompanied by serious complications such as intestinal stricture, perforation, and even cancer, significantly impairing patients' quality of life. In recent years, the global incidence of IBD has continued to rise, and the affected population is showing a trend towards younger ages. In my country, with environmental changes and lifestyle shifts during urbanization, the prevalence of IBD is also increasing year by year.

[0003] Currently, clinical treatment of IBD mainly relies on 5-aminosalicylic acid drugs, immunosuppressants, biologics, and surgery. Although novel therapies, represented by biologics, have achieved some efficacy, they still face many challenges such as high treatment costs, drug resistance, and individual variability in efficacy, placing a heavy burden on the social healthcare system. Therefore, a thorough understanding of the pathophysiology and molecular biochemical mechanisms of IBD occurrence and development is of great significance for improving the clinical diagnosis and treatment of this disease.

[0004] Malic enzyme (ME) is a key enzyme catalyzing the oxidative decarboxylation of malate to pyruvate and is also an important source of nicotinamide adenine dinucleotide phosphate (NADPH), participating in the regulation of cellular metabolism, biosynthesis, and homeostasis. Three ME isoforms have been identified in mammalian cells: cytoplasmic ME1, mitochondrial ME2, and ME3. Cytoplasmic ME1 promotes lipid and cholesterol synthesis in the liver and adipose tissue, and drives intestinal epithelial cell proliferation in the gastrointestinal tract. Studies have shown that ME1 dysfunction is closely related to the progression of various diseases, including diabetes, IBD, and tumors. In particular, ME1 overexpression in lipopolysaccharide-activated macrophages promotes the release of inflammatory mediators and exacerbates the inflammatory response, suggesting that ME1 may play an important role in IBD development as a key molecule in the pro-inflammatory function of macrophages. However, the application of the ME1 inhibitor ME1* in the prevention and treatment of IBD has not yet been systematically reported, and this field requires further in-depth exploration. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides the application of ME1 in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease. By revealing the pathological functions of ME1 in the pathogenesis of IBD that have not yet been fully elucidated, this study systematically elucidates the key role of this protein in the inflammatory regulatory network and further innovatively explores the therapeutic potential of the ME1 inhibitor ME1*.

[0006] The technical solution provided by this invention is as follows:

[0007] This invention provides the use of ME1 as a target in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease.

[0008] Furthermore, ME1 as a target refers to reducing the expression of the ME1 gene through gene knockout, gene knockdown, gene silencing, or chemical drugs.

[0009] This invention also provides the use of ME1 inhibitors in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease.

[0010] Furthermore, the ME1 inhibitor is ME1*, and the chemical structure of ME1* is shown in Formula I: ; Formula I.

[0011] Furthermore, the ME1 inhibitor is used to improve progressive weight loss caused by inflammatory bowel disease; and / or to improve colonic shortening caused by inflammatory bowel disease.

[0012] Furthermore, the ME1 inhibitor is used to improve colonic mucosal damage caused by inflammatory bowel disease; and / or to improve inflammatory cell infiltration of the colonic mucosal layer caused by inflammatory bowel disease; and / or to improve macrophage-mediated inflammatory cascade response caused by inflammatory bowel disease.

[0013] Furthermore, the inflammatory bowel disease includes Crohn's disease and ulcerative colitis.

[0014] The present invention also provides the use of substances for detecting ME1 in the preparation of diagnostic or diagnostic drugs for inflammatory bowel disease.

[0015] Furthermore, the substance for detecting ME1 includes reagents for detecting ME1 expression levels at the gene and / or protein levels.

[0016] Furthermore, the substance used to detect ME1 is a substance selected from one or more detection techniques or methods from the group consisting of: immunohistochemistry, Western blotting, Northern blotting, PCR, and microarray.

[0017] Furthermore, the immunohistochemical method is selected from one of the following: immunofluorescence assay, immunoenzyme labeling assay, and immunogold assay.

[0018] Furthermore, the reagents used to detect ME1 expression levels at the protein level include antibodies.

[0019] The present invention also provides a kit for detecting ME1, wherein the kit for detecting ME1 contains a substance for detecting ME1.

[0020] The present invention also provides a method for inhibiting macrophage pyroptosis, characterized in that macrophages are transfected with ME1-specific siRNA, thereby inhibiting macrophage pyroptosis.

[0021] Furthermore, the nucleotide sequence of the ME1-specific siRNA is as follows: sense strand: 5'-CCAGGUUCUUAGAGUAGUATT-3'; antisense strand: 5'-UACUACUCUAAGAACCUGGTT-3'.

[0022] Beneficial effects

[0023] This invention analyzed 30 normal tissue samples, 38 ulcerative colitis tissue samples, and 50 Crohn's disease tissue samples using immunohistochemical staining to assess the difference in ME1 expression between inflammatory bowel disease (IBD) tissues and normal tissues. Statistical analysis using GraphPad Prism software confirmed that ME1 expression levels in IBD were significantly positively correlated with both the Crohn's Disease Activity Index (CDAI) and the degree of mucosal damage (Mayo score). These results further support the diagnostic value of ME1 as a potential biomarker for IBD.

[0024] This invention proposes the application of a substance for detecting ME1 in the preparation of diagnostic or diagnostic drugs for inflammatory bowel disease (IBD). Given the significant positive correlation between ME1 expression levels and the risk of developing IBD, this detection substance can achieve precise quantification of ME1 expression, thus providing a reliable basis for the diagnosis of IBD and holding the potential to be integrated into the current diagnostic system as an effective diagnostic indicator, providing a crucial reference for clinical diagnosis. Furthermore, the detection platform involved in this invention integrates high-throughput detection technology, enabling efficient analysis of large-scale clinical samples, and powerfully promoting the clinical translation and application of IBD diagnostic technology.

[0025] To verify the role of ME1 in disease progression, this invention constructed mouse models of DSS-induced ulcerative colitis and TNBS-induced Crohn's disease, and intervened by intraperitoneal injection of the ME1-specific inhibitor ME1*. Results showed that mice in both the DSS and TNBS treatment groups exhibited typical colitis symptoms, including progressive weight loss and colonic shortening; ME1* treatment significantly improved these pathological phenotypes. Histopathological analysis revealed extensive destruction of the colonic mucosa in the model group mice, accompanied by extensive inflammatory cell infiltration and ulceration; in contrast, the colonic mucosa structure of the ME1* treatment group mice remained relatively intact, and inflammatory cell infiltration was significantly reduced. Further immunofluorescence staining results showed a significant decrease in the density of IL-1β-positive cells in the colonic tissue of the ME1* treatment group mice, and the expression of the macrophage activation marker F4 / 80 was also inhibited, suggesting that inhibiting ME1 function can specifically regulate the macrophage-mediated inflammatory cascade response. These experimental results collectively demonstrate that the ME1-specific inhibitor ME1* has a significant therapeutic effect on inflammatory bowel disease.

[0026] Scanning electron microscopy revealed that decreased ME1 expression reduced pyroptosis, decreased cell surface pores, and alleviated cell swelling. ELISA analysis showed that in the pyroptosis-induced cell group, the secretion of inflammatory factors IL-6 and IL-1β was significantly increased, and this phenomenon could be reversed by interfering with ME1 expression. Attached Figure Description

[0027] Figure 1 The expression of ME1 differs between patients with inflammatory bowel disease (IBD) and normal tissues. (A) Representative immunohistochemical images show that ME1 protein expression was significantly upregulated in colon tissues of patients with ulcerative colitis (n=38) and Crohn's disease (n=50) compared with healthy controls (n=13) (scale bar: 100 μm). (B) Correlation analysis showed that the expression level of ME1 in colon tissues of IBD patients was significantly positively correlated with the Crohn's disease activity index (CDAI) and Mayo score.

[0028] Figure 2 The therapeutic effects of the ME1 inhibitor ME1* on DSS and TNBS-induced colitis in mice are shown. Among them, (AC) ME1 intervention significantly improved the gross morphology of the colon (A), the trend of weight loss (B), and the colon shortening phenomenon (C) in mice with DSS-induced colitis. (DF) In the TNBS-induced colitis model, ME1 treatment also alleviated the changes in colon morphology (D), weight loss (E), and colon shortening (F). (GH) H&E staining of colon tissue showed that the mucosal structure of the model group was severely damaged and accompanied by a large number of inflammatory cells infiltrating, while the inflammatory infiltration of the ME1* treatment group was reduced and the mucosal structure was more intact (scale bar: 100 μm).

[0029] Figure 3 The study investigated the regulatory effect of ME1* on the expression of inflammatory factors in colitis mice. (A) Immunofluorescence staining showed that the colocalization signal of IL-1β (red) and macrophage marker F4 / 80 (green) in the colonic tissue of DSS model mice was significantly reduced after ME1* treatment (DAPI nuclei, blue; scale bar: 100 m); (B) Protein level detection further confirmed that ME1* can reduce the expression of IL-1β in the colonic tissue of colitis mice.

[0030] Figure 4 The effect of ME1 knockdown on macrophage pyroptosis morphology was investigated. After induced pyroptosis, macrophages exhibited typical morphological changes, including increased cell surface pores and significant swelling. Knockdown of ME1 expression reduced the degree of pyroptosis, decreased pore formation, and alleviated cell swelling.

[0031] Figure 5 The effect of ME1 knockdown on the secretion of inflammatory factors in pyroptosis-induced macrophages: In pyroptosis-induced macrophages, ME1 knockdown significantly inhibited the expression of inflammatory factors IL-6 (A) and IL-1β (B). Detailed Implementation

[0032] To help those skilled in the art gain a deeper understanding of the present invention, the technical details of the present invention will be described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the embodiments described only cover a part of the present invention, not all of it. Those skilled in the art can derive other feasible solutions based on these embodiments without creative effort, and all such solutions should be included within the protection scope of the present invention. Subsequently, this document will provide a comprehensive analysis of the present invention through the organic combination of the accompanying drawings and embodiments.

[0033] Example 1

[0034] Immunohistochemical staining method to detect ME1 expression in the colon of patients with inflammatory bowel disease.

[0035] This study used immunohistochemical staining to detect the expression of ME1 in the colonic tissue of IBD patients. Human tissue samples used in the experiment (including 30 normal colonic tissue samples, 38 ulcerative colitis tissue samples, and 50 Crohn's disease tissue samples) were all obtained from the First Affiliated Hospital of Soochow University. Informed consent was obtained from all patients before the collection of all samples.

[0036] The immunohistochemical staining reagents used were: ME1 primary antibody (rabbit anti-human / mouse ME1 polyclonal antibody, Proteintech, catalog number: 16619-1-AP, dilution 1:100), universal mouse and rabbit HRP secondary antibody (Fuzhou Maixin Biotechnology Co., Ltd.), and DAB substrate (CST, catalog number: #8059, Danvers).

[0037] Immunohistochemical staining steps:

[0038] (1) Dewaxing and hydration of slides: After the slide rack is loaded with the sample, it is placed in a 65°C thermal cycling oven for 60 min to cure. Then it is placed in xylene I for 15 min and xylene II for 10 min. Then it is hydrated in stages of 3 min (95% ethanol → 85% ethanol → 75% ethanol → ddH2O rinsing → PBS buffer soaking).

[0039] (2) Antigen epitope retrieval: After preparing sodium citrate buffer (1.5g: 500mL), put it into a pressure cooker. When bubbles emerge from the retrieval solution, put the tissue specimen section into the retrieval solution. After the pressure cooker releases steam, boil for 5 minutes. Remove the pressure cooker and let it cool with running water for 30 minutes after the pressure is released naturally. Then wash it repeatedly with ddH2O 3 times, 3 minutes each time.

[0040] (3) Tissue blocking pretreatment: After drying the tissue slide, circle the tissue specimen with an immunohistochemical waterproof pen, add endogenous peroxidase inhibitor to the slide in sequence, and place it at room temperature in the dark for 10 minutes. Then rinse with PBS 3 times, 3 minutes each time.

[0041] (4) Non-specific binding blocking: After the tissue is fully immersed in the goat serum blocking solution, it is placed in a constant temperature incubator at 37°C for 30 min and then directly enters the primary antibody reaction without washing.

[0042] (5) Specific antigen-antibody reaction: Add ME1 primary antibody dilution (1:100), incubate overnight at 4°C (≥16h), then remove the humidified box from the refrigerator, warm it at room temperature for 30min, remove the ME1 primary antibody dilution from the slide, wash with PBS 3 times, 3min each time, after drying the slide, add rabbit universal HRP secondary antibody, incubate at 37°C for 30min, remove the secondary antibody, wash with PBS 3 times again, 3min each time.

[0043] (6) DAB development: Add freshly prepared DAB working solution (1:20) to immerse the tissue, monitor the development process under a microscope for 2 minutes, then immediately remove the developing solution, place the tissue in pure water to stop the development, and rinse under running water for 5 minutes.

[0044] (7) Hematoxylin counterstaining: Add hematoxylin staining solution to immerse the tissue, control the reaction time to 2 min, and then rinse under running water to reverse the blue staining.

[0045] (8) Specimen solidification and preservation: First, dehydrate the tissue slides in a gradient for 1 min / step (75% ethanol → 95% ethanol → anhydrous ethanol → xylene I → xylene II).

[0046] (9) Covering the tissue with neutral resin, leaving no air bubbles, and then place the tissue in a fume hood to dry.

[0047] Interpretation and scoring of immunohistochemical staining results

[0048] ImageJ software was used to analyze the histochemical images, which were acquired under high magnification. Cell staining intensity was initially scored as 0 (colorless), 1 (pale yellow), 2 (brownish-yellow), and 3 (brownish-black), with 0-1 points defined as low expression and 2-3 points as high expression. The ME1 staining intensity was then quantitatively scored by multiplying the staining intensity by the proportion of each intensity level in each tissue field, with a minimum of 0 and a maximum of 300. This score was the average of two scores completed by two researchers. Results are shown below. Figure 1 .

[0049] Statistical analysis using GraphPad Prism software confirmed the correlation between ME1 expression levels in ulcerative colitis and Crohn's disease and Mayo scores and CDAI indices.

[0050] Results: This study analyzed colonic tissue specimens from 38 patients with ulcerative colitis, 50 patients with Crohn's disease, and 13 healthy controls using immunohistochemistry. The results showed that the expression level of ME1 protein in the colonic tissues of patients with ulcerative colitis and Crohn's disease was significantly increased compared with the healthy control group. Further correlation analysis indicated that the expression intensity of ME1 was positively correlated with the Mayo Cognitive Assessment (MCA) score of patients with ulcerative colitis and the Disease Activity Index (CDAI) of patients with Crohn's disease. Figure 1 ).

[0051] Example 2

[0052] ME1 inhibitor ME1* improves inflammation in mice with DSS-induced and TNBS-induced colitis.

[0053] 1. Reagents and materials

[0054] (1) Mice: C57BL / 6J mice and BALB / C mice (purchased from the Experimental Animal Center of Soochow University) were raised to about 20g in an SPF environment.

[0055] (2) Sodium dextran sulfate (DSS, #160110, purchased from MP Biomedicals, USA); trinitrobenzenesulfonic acid (TNBS, #2508-19-2ME1, purchased from Sigma-Aldrich, USA); inhibitor ME1* (purchased from Med ChemExpress, USA), with the molecular formula C 20 H 21 N3O3, CAS number 522649-59-8, molecular weight 351.40, purity 99.69%. The chemical structure of the inhibitor ME1* is shown in Formula I:

[0056] Formula I

[0057] 2. Experimental Methods

[0058] (1) Construction of DSS mouse model: Female C57BL / 6 mice aged 6-8 weeks were selected, and a 2.5% solution of DSS with a molecular weight of 36-50 kDa was prepared. The 2.5% DSS solution was used as the only drinking water and was given to the mice for 7 consecutive days to construct a 2.5% DSS-induced colitis mouse model. The experimental mice were divided into 3 groups: control group, DSS group and DSS + 3 mg / kg ME1* group, 5 mice / group. The mice were acclimatized for 7 days, and their diet, activity, defecation and urination were observed and their weight was measured. The DSS group and the DSS + 50 mg / kg ME1* group were given 3% DSS solution as pathogenic intervention for 7 consecutive days; the control group was given sterile distilled water for 7 days; the DSS + 50 mg / kg ME1* group was given 50 mg / kg ME1* 100 uL by intraperitoneal injection on days 0, 2, 4 and 6 of modeling. Observe the mice daily for fecal occult blood, fecal characteristics, degree of weight loss, and survival.

[0059] (2) Construction of TNBS mouse model: Prepare TNBS solution by dissolving TNBS at a concentration of 5 mg / mL in 50% ethanol solution to prepare a 2.5% TNBS solution. Mildly anesthetize mice and slowly inject 100 uL of the 2.5% TNBS solution into the anus through a catheter, keeping the mice in a head-down position for 30-60 seconds to prevent leakage. Use an equal volume of ethanol as a solvent control and physiological saline as a blank control. Experimental mice were divided into 3 groups: control group, TNBS group, and TNBS + 50 mg / kg ME1* group, 5 mice per group. Mice were acclimatized for 7 days, and their diet, activity, defecation and urination were observed and their weight was measured. On days 0, 2, 4, and 6 of model establishment, the TNBS group and the TNBS + 50 mg / kg ME1* group were given 100 uL of 50 mg / kg ME1* via intraperitoneal injection. The fecal occult blood, characteristics, weight loss, and survival of the mice were observed daily.

[0060] (3) Sample collection and processing: Mice were sacrificed on day 7 of modeling, and the complete colonic segment from the rectum to the ileocecal junction was isolated. The colonic length was measured and recorded. Distal colonic tissue was taken, some of which was immediately stored at -80℃ for later use, and some was fixed for immunofluorescence and HE detection.

[0061] 3. Experimental Results

[0062] This study successfully induced mouse colitis models using 2.5% DSS and 2.5% TNBS, respectively, and intervened with the ME1-specific inhibitor ME1* (50 mg / kg). The results showed that, compared with the control group, mice in both the DSS and TNBS model groups exhibited typical colitis, characterized by progressive weight loss and significant shortening of the colon. ME1* treatment effectively alleviated the above pathological phenotypes. Figure 2 (A–F).

[0063] HE staining showed that the colonic mucosa structure of the model group mice was severely damaged, accompanied by a large number of inflammatory cell infiltrations and ulcer formation; while the integrity of the colonic mucosa in the ME1* treatment group was well maintained, and the degree of inflammatory infiltration was significantly reduced. Figure 2 G, H).

[0064] Further immunofluorescence staining revealed a significant decrease in the density of IL-1β-positive cells in the colon tissue of the ME1* treatment group, and the expression of the macrophage marker F4 / 80 was also inhibited. Figure 3 These results suggest that inhibiting ME1 function can specifically regulate macrophage-mediated inflammatory cascade responses, thereby alleviating intestinal inflammatory damage.

[0065] Example 3

[0066] Inhibitory effect of ME1 gene knockout on macrophage pyroptosis and inflammatory cytokine production

[0067] 1. Reagents and materials

[0068] (1) Cells: THP-1 cells (purchased from ATCC, USA) and macrophages (MDM) derived from human peripheral blood mononuclear cells.

[0069] (2) Reagents and kits: LPS (purchased from Med Chem Express, USA) and Nigerian styracin (purchased from Med Chem Express, USA). IL-1β ELISA kit (purchased from Thermo Fisher Scientific, USA) and IL-6 ELISA kit (purchased from Meimian Biotechnology, China). Lipofectamine 2000 (purchased from Invitrogen, USA). siRNA sequences, namely Si-ME1 and control si-NC (purchased from Suzhou Jima Biotechnology Co., Ltd., China).

[0070] Si-ME1: Chain of Justice: 5'-CCAGGUUCUUAGAGUAGUATT-3' (SEQ ID NO.1); Antisense chain: 5'-UACUACUCUAAGAACCUGGTT-3' (SEQ ID NO.2).

[0071] Si-NC: Chain of Justice: 5'-UUCUCCGAACGUGUCACGUTT-3' (SEQ ID NO.3); Antisense chain: 5'-ACGUGACACGUUCGGAGAATT-3 (SEQ ID NO.4).

[0072] 2. Experimental Grouping

[0073] The experiment was divided into 4 groups: Si-NC (the control sequence was introduced into the cells and pyroptosis was not induced), Si-ME1 (the ME1 gene was knocked down in the cells and pyroptosis was not induced), Si-NC-pyroptosis (the control sequence was introduced into the cells and pyroptosis was induced), and (the ME1 gene was knocked down in Si cells and pyroptosis was induced).

[0074] 3. Experimental Methods

[0075] (1) Dilute 20 pmol siRNA in a sterile EP tube with 50 µL of Opti-MEM® I serum-free medium. Mix gently.

[0076] (2) In another EP tube, dilute 1.0 µL of Lipofectamine 2000 with 50 µL of Opti-MEM® I serum-free medium. Mix gently and let stand at room temperature for 5 minutes.

[0077] (3) Gently mix the two diluents and let stand at room temperature for 20 minutes to form a transfection complex.

[0078] (4) Add 100 µL of the transfection complex dropwise to the cell culture wells that have been replaced with fresh antibiotic-free complete culture medium. Gently shake the culture plate to mix.

[0079] (5) The transfected THP-1 and MDM cells were placed back into a 37°C, 5% CO2 incubator and cultured for 24 hours.

[0080] (6) The pyroptosis model was constructed by stimulating the cells with 200 ng / mL LPS for 4 hours and then with 10 µM Nigerian cytosine for 30 minutes.

[0081] (7) All cells were cultured in a humid incubator at 37°C and 5% CO2.

[0082] (8) Use scanning electron microscopy to observe the morphological changes of cells after pyroptosis.

[0083] (9) The effects of ME1 knockdown on IL-1β and IL-6 levels were analyzed using the ELASA experiment.

[0084] 4. Experimental Results

[0085] This study successfully established a macrophage pyroptosis model using THP-1 and MDM cells, and explored the effect of ME1 downregulation on the pyroptosis process. Scanning electron microscopy results showed that, compared with the pyroptosis model group, the ME1 knockdown group exhibited significantly reduced characteristic pyroptosis morphologies (such as cell surface pore formation and cell swelling). Figure 4 ELISA analysis further showed that pyroptosis induction significantly promoted the secretion of inflammatory factors IL-6 and IL-1β, while interference with ME1 expression effectively reversed this effect. Figure 5 ).

[0086] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. Application of ME1 as a target in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease.

2. The application according to claim 1, characterized in that, ME1 as a target refers to methods such as gene knockout, gene knockdown, gene silencing, or chemical drugs to reduce the expression of the ME1 gene.

3. Application of ME1 inhibitors in the preparation of drugs for the prevention and / or treatment of inflammatory bowel disease.

4. The application according to claim 3, characterized in that, The ME1 inhibitor is ME1*, and the chemical structure of ME1* is shown in Formula I: ； Formula I.

5. The application according to claim 4, characterized in that, The ME1 inhibitor is used to improve progressive weight loss caused by inflammatory bowel disease; and / or to improve colonic shortening caused by inflammatory bowel disease.

6. The application according to claim 4, characterized in that, The ME1 inhibitor is used to improve colonic mucosal damage caused by inflammatory bowel disease; and / or to improve inflammatory cell infiltration of the colonic mucosa caused by inflammatory bowel disease; and / or to improve macrophage-mediated inflammatory cascades caused by inflammatory bowel disease.

7. Application of substances that detect ME1 in the preparation of drugs for the diagnosis or detection of inflammatory bowel disease.

8. The application according to claim 7, characterized in that, The substance used to detect ME1 includes reagents for detecting ME1 expression levels at the gene and / or protein levels.

9. The application according to claim 8, characterized in that, The substance used to detect ME1 is a substance selected from one or more detection techniques or methods from the group consisting of: immunohistochemistry, Western blotting, Northern blotting, PCR, and microarrays.

10. A method for inhibiting macrophage pyroptosis, characterized in that, Macrophages were transfected with ME1-specific siRNA to inhibit macrophage pyroptosis.

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