基于肠道菌群调控肠上皮细胞ERS/UPR信号通路探讨疏肝健脾法治疗溃疡性结肠炎肠黏膜屏障损伤的机制

Patients with ulcerative colitis (UC) is a serious bowel disease which does much damage to health. . Previous research has shown that the Shugan Jianpi Method（Soothing the Liver and Invigorating the Spleen）for the treatment of is effective in stimulating the UC model intestinal mucosal immunity of rats, , but the relationship between its immunity and the regulation of intestinal flora remains unclear. Intestinal flora disorder could lead to endoplasmic reticulum stress (ERS) of the intestinal mucosa epithelial cells mediated by unfolded protein response (UPR) pathway accelerate intestinal mucosal immune system development and regulation of the double function of intestinal mucosa barrier, was which could hense cause intestinal mucosa barrier damage, intestinal flora imbalance and intestinal mucosal immune disorders. Traditional studies has shown that the Shugan Jianpi Method has significant effects of regulating part of intestinal flora and intestinal mucosal immunity of rats with the UC model. According to further research literature, intestinal flora imbalance leads to intestinal mucosa barrier damage and induces its immune system disorders by stimulating endoplasmic reticulum stress(ERS), which is mediated by unfolded protein response of intestinal epithelial cells. Based on the above research, the hypothesis on “improving intestinal flora imbalance, regulating signaling pathway of enterocyte’s ERS/UPR and protecting intestinal mucosa barrier with interventional mechanism by the Shugan Jianpi Method ” has been constructed. The project, with rats of hepatic stagnation and splenic deficiency type as subjects, attempts to interpret the molecular mechanism of intervention by Shugan Jianpi Method to explore the specific intestinal flora, analyze the changes of expression of pathway through metagenomics, bioinformatic analysis, western blotting and regular quantitative PCR, explore the new target for the treatment of UC with Chinese medicine and probe a new idea for developing Chinese patent medicine of comprehensively curative effects.

溃疡性结肠炎（UC）是严重危害患者健康的疑难肠病,其发病与肠道菌群失衡密切相关。前期研究表明，疏肝健脾法治疗UC疗效确切，对UC大鼠肠黏膜免疫具有良好的调节作用，并可调节部分肠道菌群，但具体作用途径不清。研究发现，肠道菌群紊乱可激发肠上皮细胞未折叠蛋白反应（UPR）途径介导的内质网应激（ERS），使肠黏膜屏障损伤及诱发肠粘膜免疫功能紊乱。基于此，项目提出“疏肝健脾法干预UC的机制可能与其改善肠道菌群失衡，进而调控肠上皮细胞ERS/UPR信号途径，从而保护肠粘膜屏障相关”的假说。拟以肝郁脾虚型UC大鼠模型为研究对象，采用元基因组学、RT-PCR、生物信息学分析等多种方法，挖掘出疏肝健脾法可能调节的特异性的肠道菌群，并分析其对肠上皮细胞ERS/UPR信号通路相关因子表达的影响，从而系统阐释疏肝健脾法干预UC发生的分子机制。探索中医药治疗UC的新靶点，为开发具有整体调节优势的中成药提供新思路。

溃疡性结肠炎（UC）是严重危害患者健康的疑难肠病，其发病与肠道菌群失衡密切相关。前期研究表明，疏肝健脾法治疗UC疗效确切，对UC大鼠肠黏膜免疫具有良好的调节作用，并可调节部分肠道菌群，但具体作用途径不清。研究发现，肠道菌群紊乱可激发肠上皮细胞未折叠蛋白反应（UPR）途径介导的内质网应激（ERS），使肠黏膜屏障损伤及诱发肠粘膜免疫功能紊乱。基于此，项目提出“疏肝健脾法干预UC的机制可能与其改善肠道菌群失衡，进而调控肠上皮细胞ERS/UPR信号途径，从而保护肠粘膜屏障相关”的假说。拟以肝郁脾虚型UC大鼠模型为研究对象，采用元基因组学、RT-PCR、生物信息学分析等多种方法，挖掘出疏肝健脾法可能调节的特异性的肠道菌群，并分析其对肠上皮细胞ERS/UPR信号通路相关因子表达的影响，从而系统阐释疏肝健脾法干预UC发生的分子机制。探索中医药治疗UC的新靶点，为开发具有整体调节优势的中成药提供新思路。