基于肠道菌群和TLR4/MyD88信号通路调控的黄芩汤对溃疡性结肠炎肠粘膜屏障保护作用的机制研究

项目名称： 基于肠道菌群和TLR4/MyD88信号通路调控的黄芩汤对溃疡性结肠炎肠粘膜屏障保护作用的机制研究

项目编号： No.81473592

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： 杨伟鹏

作者单位： 中国中医科学院中药研究所

项目金额： 74万元

中文摘要： 肠道菌群对溃疡性结肠炎（UC）发病有至关重要的影响，NF-κ B信号通路与UC发病关系密切，TLR4是NF-κ B信号通路调控的重要的上游通路，MyD88是TLRs关键接头蛋白信号，TLR4/ MyD88信号通路在溃疡性结肠炎的发病机制及治疗中起着极为重要的作用。基于黄芩汤治疗UC显著的临床疗效、现代药理以及前期工作基础，提出黄芩汤对于UC的治疗是对于包括肠道菌群调节、TLR4和MyD88信号通路等诸多因素的综合调控结果，进而发挥肠粘膜保护作用。本项目从体内外两方面，采用微生物研究技术和分子生物学技术，分析UC模型肠道菌群数量、种类和DNA指纹图谱的变化，TLR4、NF-κ B信号通路基因和蛋白表达、相关炎性因子的变化以及肠道菌群与TLR4/ MyD88信号通路作用的相关性分析，来阐明黄芩汤治疗UC多通路、多靶点的作用机制并诠释中医辨证治疗的整体观思想。

中文关键词： 黄芩汤；肠道菌群；Toll样受体；髓样分化因子88；溃疡性结肠炎

英文摘要： Intestinal flora have very important influence to ulcerative colitis (UC) disease, the nf-kappa B signaling pathways closely associated with the onset of UC, TLR4 is important upstream pathways regulating the nf-kappa B signaling pathways, MyD88 protein is a key sub TLRs signals, TLR4 / MyD88 signaling pathways in the pathogenesis and treatment of ulcerative colitis plays an extremely important role. Based on the clinical curative effect of huangqintang treatment of UC, modern pharmacology and prophase work foundation, huangqintang for the treatment of UC is put forward for regulation, including the intestinal flora of TLR4 and MyD88 signaling pathways integrated control of many factors, such as a result, thus play a role of intestinal mucosal protection. This project from both in vivo and in vitro, using microbial research techniques and molecular biology techniques, intestinal flora analysis UC model number, type, and the change of DNA fingerprint, TLR4, the nf-kappa B pathway gene and protein expression, the change of related inflammatory cytokines and intestinal flora and correlation analysis of the role of TLR4 / MyD88 signaling pathways, to clarify scutellaria decoction in the treatment of UC pathway and the mechanism of action of target and the overall concept of interpretation of traditional Chinese medicine syndrome differentiation treatment ideas.

英文关键词： huangqintang;intestinal flora;Toll-like receptors;myeloid differentiation factor 88;ulcerative colitis