针灸阻抑克罗恩病肠纤维化上皮间质转化的分子调控机制

项目名称： 针灸阻抑克罗恩病肠纤维化上皮间质转化的分子调控机制

项目编号： No.81473757

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 施茵

作者单位： 上海中医药大学

项目金额： 74万元

中文摘要： 肠纤维化是目前克罗恩病(CD)中常见且治疗最为棘手的难题。本项目在课题组以往大量针灸治疗CD及肠纤维化有效的基础上，以肠上皮间质转化可引发或导致CD肠纤维化为切入点，运用组织学、细胞学及分子生物学等技术，试图从体外细胞水平、在体动物实验与临床观察多层面相结合研究：①拟证实介导CD肠道慢性炎症与损伤修复的主要介质TNF-α和TGF-β1表达异常，两者分别通过TNF-α-NF-κB-SNAIL和TGF-β1-Smads-SNAIL途径所致的肠上皮间质转化是引发或导致CD肠纤维化的主要环节之一；同时证明转录因子SNAIL能够抑制CD肠上皮主要标志物的表达是这二条途径肠上皮间质转化中的重要调控蛋白；②初步阐明针灸可能是通过抑制CD肠组织TNF-α、TGF-β1的异常表达进而阻遏这二条途径所致的肠上皮间质转化，由此达到阻抑CD肠纤维化效应，以期为针灸治疗CD及肠纤维化的效应机制研究提供科学依据。

中文关键词： 克罗恩病；针灸疗法；上皮间质转化；肠纤维化；调控机制

英文摘要： Intestinal fibrosis is the common while the most intractable problem in Crohn's disease (CD). Based on a large number of previous effective acupuncture treatments for Crohn's disease and intestinal fibrosis, this research group takes intestinal epithelial-mesenchymal transition can initiate or result in the testinal fibrosis in Crohn's disease as the cut point. Histological, cellular, molecular biological and other techniques are applied to research from cellular level in vitro, whole animal experiments and clinical observation for the following purposes: ① To confirm that Obviously abnormal expressions of the major media tumor necrosis factor-alpha(TNF-alpha)and transforming growth factor-β1(TGF-β1) of Crohn's disease-mediated chronic inflammation and damaging repair cause intestinal epithelial-mesenchymal transition through TNF-alpha-nuclear factor κB(NF-κB)-SNAIL and TGF-β1-Smads-SNAIL pathways and initiate or result in the testinal fibrosis in Crohn's disease; to prove that transcription factor SNAIL can inhibit the expression of Crohn's disease intestinal epithelial markers and is an important regulatory protein in intestinal epithelial-mesenchymal transition of these two pathways; ② To clarify that acupuncture may deter the intestinal fibrosis of Crohn's disease through inhibition of intestinal epithelial-mesenchymal transition of these two pathways by inhibiting the abnormal TNF-alpha and TGF-β1 expression, and expect to provide the scientific evidence for the effect mechanism of acupuncture and moxibustion therapy for Crohn's disease and intestinal fibrosis.

英文关键词： Crohn's disease;Acupuncture and Moxibustion therapy;Epithelial-mesenchymal transition;Intestinal fibrosis;Regulation mechanism