CN-122005567-A - Application of ME1 in preparation of medicines 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 medicines for preventing and/or treating inflammatory bowel diseases. The invention discloses an application of an ME1 inhibitor in preparing a medicament for preventing and/or treating inflammatory bowel disease, and an application of a substance for detecting ME1 in preparing a medicament for diagnosing or detecting inflammatory bowel disease. The invention evaluates the effect of ME1 in disease treatment through a mouse IBD model induced by dextran sodium sulfate DSS and trinitrobenzene sulfonic acid TNBS, thereby providing a new strategy and method for clinical intervention of IBD. In addition, the invention also defines the application of ME1 as a high-specificity biomarker in IBD diagnosis, and further expands the comprehensive value of the ME1 in disease prevention and treatment.

Inventors

• SHI TONGGUO
• ZHANG HUAN
• CHEN YUEQIU

Assignees

• 苏州大学附属第一医院

Dates

Publication Date

20260512

Application Date

20260128

Claims (10)

1. Use of me1 as target in the preparation of a medicament for the prevention and/or treatment of inflammatory bowel disease.
2. 2. The use according to claim 1, wherein ME1 is targeted by comprising reducing ME1 gene expression using gene knockout, gene knockdown, gene silencing or a chemical agent.
3. Use of an inhibitor of me1 for the preparation of a medicament for the prevention and/or treatment of inflammatory bowel disease.
4. 4. The use according to claim 3, wherein the ME1 inhibitor is ME1, and the chemical structure of ME1 is as shown in formula I: ; Formula I.
5. 5. The use according to claim 4, wherein the ME1 inhibitor is used for improving the progressive weight loss caused by inflammatory bowel disease and/or for improving the colon shortening caused by inflammatory bowel disease.
6. 6. The use according to claim 4, wherein the ME1 inhibitor is used for improving colonic mucosal layer destruction caused by inflammatory bowel disease, and/or for improving colonic mucosal layer inflammatory cell infiltration caused by inflammatory bowel disease, and/or for improving macrophage-mediated inflammatory cascade caused by inflammatory bowel disease.
7. 7. Use of a substance for detecting ME1 in the preparation of a medicament for diagnosis or detection of inflammatory bowel disease.
8. 8. The use according to claim 7, wherein the substance for detecting ME1 comprises an agent for detecting the expression level of ME1 at the gene level and/or protein level.
9. 9. The use according to claim 8, wherein the substance for detecting ME1 is a substance for use in one or more detection techniques or methods selected from the group consisting of immunohistochemistry, western blotting, northern blotting, PCR, biochip method.
10. 10. A method for inhibiting macrophage pyrosis, comprising transfecting macrophages with a specific siRNA directed against ME1, thereby inhibiting macrophage pyrosis.

Description

Application of ME1 in preparation of medicines for preventing and/or treating inflammatory bowel disease Technical Field The invention belongs to the technical field of biomedicine, and relates to an application of ME1 in preparing medicines for preventing and/or treating inflammatory bowel diseases. Background Inflammatory bowel Disease (Inflammatory Bowel Disease, IBD) is a group of diseases characterized by chronic gastrointestinal inflammation, mainly including Crohn's Disease (CD) and ulcerative colitis (uLcerative Colitis, UC). It is typically manifested as recurrent abdominal pain, diarrhea and weight loss, and can be accompanied by severe complications such as intestinal stenosis, perforation, and even cancer, significantly compromising the quality of life of the patient. In recent years, the prevalence of IBD has continuously risen worldwide, and the pathogenic population has shown a tendency to younger. In China, along with environmental changes and life style changes in the process of urbanization, the prevalence of IBD is also increasing year by year. At present, the clinical treatment of IBD mainly depends on means such as 5-aminosalicylic acid medicines, immunosuppressants, biological agents, surgical operations and the like. Although the novel therapies represented by biological agents achieve a certain curative effect, the novel therapies still face a plurality of challenges such as high treatment cost, drug resistance and individual curative effect difference, and the like, and bring a heavy burden to a social medical system. Therefore, the pathophysiology and molecular biochemistry mechanism of IBD occurrence and development are deeply clarified, and the method has important significance for improving the clinical diagnosis and treatment level of the disease. Malic Enzyme (ME) is a key Enzyme catalyzing oxidative decarboxylation of Malic acid to pyruvate, and is one of important sources of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) to participate in regulating cell metabolism, biosynthesis and maintenance of homeostasis. Three ME subtypes have been identified in mammalian cells, cytoplasmic ME1, mitochondrial ME2 and ME3, respectively. Wherein, the cytoplasmic ME1 promotes the synthesis of lipid and cholesterol in liver and adipose tissue, and drives intestinal epithelial cell proliferation in gastrointestinal tract tissue. Studies have shown that ME1 dysfunction is closely related to the progression of various diseases such as diabetes, IBD and tumors. In particular, in lipopolysaccharide activated macrophages, ME1 overexpression promotes inflammatory mediator release, exacerbates inflammatory response, suggesting that ME1 may play an important role in IBD development as a key molecule for macrophage pro-inflammatory action. However, no systematic report has been made about the application of ME1 inhibitors ME1 in IBD control, and this field has yet to be further explored. Disclosure of Invention In order to overcome the defects of the prior art, the invention provides the application of ME1 in preparing medicines for preventing and/or treating inflammatory bowel diseases, and by revealing the pathological functions of ME1 which are not fully elucidated in the IBD pathogenesis, the research system explains the key position of the protein in an inflammation regulation network, and further innovatively explores the treatment potential of ME1 inhibitor ME 1. The technical scheme provided by the invention is as follows: The invention provides an application of ME1 serving as a target in preparing a medicament for preventing and/or treating inflammatory bowel disease. Further, ME1 is targeted and is meant to include the use of gene knockouts, gene knockdown, gene silencing, or chemical agents to reduce the expression of the ME1 gene. The invention also provides application of the ME1 inhibitor in preparing medicines for preventing and/or treating inflammatory bowel diseases. Further, the ME1 inhibitor is ME1, and the chemical structure of ME1 is shown in formula I: ; Formula I. Further, the ME1 inhibitor is used for improving the progressive weight loss caused by inflammatory bowel disease and/or for improving colon shortening caused by inflammatory bowel disease. Further, the ME1 inhibitor is used for improving the destruction of colonic mucosa caused by inflammatory bowel disease, and/or for improving inflammatory cell infiltration of colonic mucosa caused by inflammatory bowel disease, and/or for improving macrophage-mediated inflammatory cascade reaction caused by inflammatory bowel disease. Further, the inflammatory bowel disease includes crohn's disease and ulcerative colitis. The invention also provides application of the ME1 detection substance in preparing inflammatory bowel disease diagnosis or detection medicines. Further, the substance for detecting ME1 comprises an agent for detecting the expression level of ME1 at the gene level and/or the protein level. Further, the sub