通过“肠道菌群移植”重建粘膜免疫稳态对非酒精性脂肪性肝炎的防治研究

项目名称： 通过“肠道菌群移植”重建粘膜免疫稳态对非酒精性脂肪性肝炎的防治研究

项目编号： No.81470840

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： 范建高

作者单位： 上海交通大学

项目金额： 75万元

中文摘要： 近年来非酒精性脂肪性肝炎（nonalcoholic steatohepatitis, NASH）发病率不断增高，已成为我国的重要肝病之一。国内外研究显示，高脂饮食导致的肠道菌群结构紊乱可能破坏肠粘膜免疫稳态，并募集肠道的活化淋巴细胞向肝脏归巢，进而诱发NASH。为此，本研究尝试在高脂饮食诱导小鼠NASH模型基础上，通过肠道菌群移植恢复正常的肠道菌群结构；观察肠道菌群调控对纠正肠粘膜Th1/Th2、Th17/Treg细胞比例，抑制肠-肝间淋巴细胞归巢/再循环，以及阻断肝脏免疫反应的作用。以期揭示肠道菌群经粘膜免疫系统介导对NASH发生发展的影响及其确切机制，从而为NASH防治提供新手段。

中文关键词： 肠道菌群；移植；粘膜免疫；稳态；非酒精性脂肪性肝炎

英文摘要： The increasing incidence of nonalcoholic steatohepatitis (NASH) has qualified it to be one of the most important liver diseases in China. Abnormal fecal microbiota, which is introduced by high-fat diet (HFD), has recently been reported to induce NASH on the basis of mucosal immunity disturbance and then intestine-liver lymphocyte homing. We thus attempt to restore the fecal microbiota in HFD-induced NASH by 'fecal microbiota transplantation'. The effects of fecal microbiota regulation are evaluated by means of Th1/Th2 and Th17/Treg proportion, intestine-liver lymphocyte homing/recycle, and resultantly hepatic immune response. This research may uncover the critical role and underlying mechanisms of fecal microbiota, being mediated by mucosal immunity system, in the genesis and development of NASH, and normalization of fecal microbiota may highlight a novel prevention and treatment for NASH.

英文关键词： fecal microbiota;transplantation;mucosal immunity;homeostasis;nonalcoholic steatohepatitis