阅读说明：本技术 一种地西他滨在制备治疗炎症性肠病药物中的用途 (Application of decitabine in preparation of medicine for treating inflammatory bowel disease ) 是由 苏畅 曹奕鸥 茅安炜 饶龙华 于 2020-06-09 设计创作，主要内容包括：本发明公开了一种地西他滨在制备治疗炎症性肠病药物中的用途,所述地西他滨能够提高炎症性肠病小鼠脾脏调节性T细胞比例；能够提高炎症性肠病小鼠结肠组织中调节性T细胞相关细胞因子含量；能够提高炎症性肠病小鼠结肠组织紧密连接蛋白的表达；能够明显控制小鼠炎性肠病的结肠病变。本发明的地西他滨可诱导炎性肠病患者对肠道非致病性抗原的免疫耐受、恢复肠屏障功能,提高有效率及缓解率,降低复发率。(The invention discloses an application of decitabine in preparing a medicament for treating inflammatory bowel disease, wherein the decitabine can improve the proportion of splenic regulatory T cells of mice with inflammatory bowel disease; can improve the content of regulatory T cell related cytokines in colon tissues of mice with inflammatory bowel diseases; can improve the expression of the tight junction protein of the colon tissue of the mice with the inflammatory bowel diseases; can obviously control colon lesion of the inflammatory bowel disease of mice. The decitabine can induce immune tolerance of inflammatory bowel disease patients to intestinal non-pathogenic antigens, recover intestinal barrier function, improve effective rate and remission rate, and reduce recurrence rate.)

1. An application of decitabine in preparing a medicament for treating inflammatory bowel disease.

2. The use of decitabine as defined in claim 1, in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein: decitabine increases the proportion of splenic regulatory T cells in mice with inflammatory bowel disease.

3. The use of decitabine as defined in claim 1, in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein: decitabine increases regulatory T cell-associated cytokine levels in colon tissue of mice with inflammatory bowel disease.

4. The use of decitabine as defined in claim 1, in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein: decitabine increases the expression of tight junction protein in colon tissue of mice with inflammatory bowel disease.

5. The use of decitabine as defined in claim 1, in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein: decitabine significantly controls colonic lesions of inflammatory bowel disease in mice.

Technical Field

The invention relates to the technical field of biology, and in particular relates to application of decitabine in preparation of a medicine for treating inflammatory bowel disease.

Background

Inflammatory bowel disease generally refers to non-specific inflammatory bowel disease of unknown etiology, including ulcerative colitis and crohn's disease. The disease is more common in European and American countries, but with the remarkable increase of the number of cases reported in various hospitals in China in recent years, inflammatory bowel disease becomes a common disease in ChinaDiseases of the digestive tract. The etiology of inflammatory bowel disease is not clear, and is considered to be related to genetic factors, environmental factors, immunodeficiency, microbial exposure, and the like. The conventional medicines for treating inflammatory bowel diseases are sulfasalazine and infliximab, the effective rate of the sulfasalazine for treating inflammatory bowel diseases is 50-70%, the remission rate is 40-60%, and the recurrence rate is 15-30%; and infliximab is expensive. The pathological process of inflammatory bowel disease is caused by repeated immune activation of the intestinal immune system against non-pathogenic antigens of the intestine, wherein regulatory T cells (tregs) play an important role in suppressing immune response, mediating immune tolerance, etc. Treg cells account for peripheral CD4 only in vivo⁺5% -10% of T cells, and small absolute quantity, and the immune tolerance can be successfully induced after the certain quantity of T cells are induced and amplified by a manual means. The high specific expression of the transcription factor Foxp3 is a determinant factor of Treg cell development and function, while the expression of Foxp3 gene is regulated by the methylation degree of CPG motif upstream of the promoter region, and the lower the methylation degree of CPG motif, the higher the expression degree of Foxp3 gene, and the more corresponding Treg cells. Decitabine (5-AZA-2' -deoxycytidine, 5AZA) is a pyrimidine nucleoside analog, and can be combined with intracellular DNA methyltransferase to form a covalent complex in the process of DNA replication, inhibit the methyl transfer activity of the enzyme, achieve demethylation, re-express genes inactivated due to methylation, recover the functions of the genes, promote the transformation of cells, and is clinically approved to be used for treating myelodysplastic syndrome and other blood system diseases.

Disclosure of Invention

The invention provides application of decitabine in preparing a medicament for treating inflammatory bowel diseases, aiming at the problems of the existing sulfasalazine and infliximab in treating inflammatory bowel diseases.

The invention is realized according to the following technical scheme.

An application of decitabine in preparing a medicament for treating inflammatory bowel disease.

Further, decitabine increases the proportion of splenic regulatory T cells in mice with inflammatory bowel disease.

Further, decitabine increases regulatory T cell-associated cytokine levels in colon tissue of mice with inflammatory bowel disease.

Further, decitabine increases the expression of tight junction protein in colon tissue of mice with inflammatory bowel disease.

Further, decitabine significantly controls colonic lesions of inflammatory bowel disease in mice.

The invention has the following beneficial effects:

the invention utilizes the demethylation effect of decitabine to reduce the methylation degree of CPG motif at the upstream of the promoter region of the Foxp3 gene, promotes the expression of Foxp3, expands Treg cells in vivo, and induces the immune tolerance of the intestinal immune system to intestinal non-pathogenic antigens, thereby treating inflammatory bowel diseases.

Drawings

FIG. 1 is a graph showing the results of flow cytometry;

FIG. 2 is a graph showing the variation of the levels of TH l 7/Treg-associated cytokines IL-17, TGF-beta and IL-10 in colon tissues of mice measured by ELISA method of the present invention;

FIG. 3 is a graph showing the expression of the immunofluorescence mapping claudin of the present invention;

FIG. 4 is a graph showing the results of scoring the disease activity index, the colon gross morphological damage index and the colon histopathology index of the mouse;

FIG. 5 is a schematic diagram of the action of decitabine of the present invention in the treatment of inflammatory bowel disease.

Detailed Description

In order to further explain the technical solutions of the present invention and the technical effects achieved by the technical solutions, the present invention will be further described with reference to the accompanying drawings and embodiments.

Modeling and treating: 3% dextran sodium sulfate is orally taken for 7 days to prepare a mouse inflammatory bowel disease model which is divided into three groups of DSS, SASP and 5AZA, and normal saline, sulfasalazine (100 mg/kg body weight) and decitabine (0.5 mg/kg body weight) are respectively injected into the abdominal cavity twice a day for 7 days of continuous treatment.