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

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.

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。

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。研究结果显示，黄芩汤可明显调控TLR4/MyD88 信号通路，进而下调促炎细胞因子NO、IL-6、TNF-α、IL-17和PGE2等的表达发挥抗炎作用；可明显调整UC模型大鼠肠道菌群中益生菌和有害菌的种属及数量变化；基于基因组学分析，筛出黄芩汤有效调节的有相互作用关系的126个基因，并发现ITGB1、FN1、CASP3、LDLR、BMP4、FABP1、ABCB1、FABP2、SLC51B等关键靶标基因，这些关键靶标基因与免疫应答、炎症、凋亡和代谢密切相关。代谢组学研究表明黄芩汤治疗溃疡性结肠炎的作用机制可能与调节氨基酸代谢、能量代谢和脂代谢等有关。