肠道菌群异常可致众多疾病，与难治性IBD的发生密切相关，且细菌鞭毛蛋白与TLR5形成的“鞭毛蛋白-TLR5炎症信号通路”对IBD病程有重要影响。而大黄牡丹汤在治疗IBD同时可改善肠道菌群。菌群代谢产物短链脂肪酸可抑制上述炎症通路，但具体靶点不明。故本项目拟在前期工作基础上，利用IBD中的UC动物模型、肠上皮细胞Caco-2和NCM460，采用HPLC、GC-MS、FCM、基因沉默、分子印迹、定量PCR和激光共聚焦等多种先进方法，研究大黄牡丹汤及大黄素、芍药苷是否通过短链脂肪酸抑制“鞭毛蛋白-TLR5炎症信号通路”发挥治疗IBD的作用，并探索短链脂肪酸抑制信号通路的具体靶蛋白。研究内容包括质控指纹图谱建立、药效评估、菌群多样性分析，以及短链脂肪酸、鞭毛蛋白、通路相关蛋白和炎症因子的检测。该项目在探讨大黄牡丹汤作用机制的同时，可加深“鞭毛蛋白-TLR5炎症信号通路”对IBD及炎症重要性的认识。

Inflammatory bowel disease (IBD), which is closely related to enteric dysbacteriosis, is mainly impacted by “Flagellin-TLR5 inflammatory signal pathway”. Rhubarb Peony Decoction (RPD), as traditional chinese medicine, could significantly improves enteric dysbacteriosis while healing IBD, Short chain fatty acids (SCFAs), as one kind of intestinal flora metabolites, suppresses the “Flagellin-TLR5 inflammatory signal pathway” with lots of confusion. IBD includes ulcerative colitis (UC) and crohn's diseases (CD), we choose UC as the disease model in our program. Therefore, to explore the mechanism of RPD, emodin and peoniflorin ameliorating IBD via inhibiting the “Flagellin-TLR5 inflammatory signal pathway” by SCFAs, and to confirm the target protein, the ulcerative colitis animal model, Caco-2 cells and NCM460 cells will be used. Advanced techniques as HPLC, GC-MS, FCM, gene silencing, western blot, qPCR and confocal will be used. The study includes establishment of fingerprint spectrum, efficacy assessment, intestinal flora diversity analysis, and also detection of SCFAs, flagellin, related proteins and inflammatory factors. This program is designed to explore the efficacy mechanism of RPD, and to show that the “Flagellin-TLR5 inflammatory signal pathway” plays an important role on IBD and inflammation.