从肠道微生态失衡探讨寒湿外邪加重类风湿关节炎的病理机制

Rheumatoid arthritis (RA) patients will appear worsen joint pain and inflammation after feelings exogenous cold damp,but the mechanism of it is not clear. Gut microbiota play an important role in maintaining the balance of immune system, and can participate in the pathogenesis of RA by regulating the balance of Th/Treg. Gut microbiota, environment and the host constitute a dynamic balance of "intestinal microecology." We infer that exogenous cold damp can cause gut microbiota imbalance, which leading to Th/Treg balance changes to aggravate the disease of RA.In this study, animal experiments are firstly conducted to explore the time-intensity and dose-effect relationship of exogenous cold damp and extinction to RA.Secondly, observe the effects of exogenous cold damp on the diversity of gut microbiota, and the relationship between key microbes with Th/Treg balance. Finally, we validate our speculation through the stool transplantation means.This project can use the modern microbiology, molecular biology method to verify the TCM theory of “Exogenous lead to disease”.It is important to further reveal the pathogenesis and risk factors of RA, and to improve the prognosis of this disease.

类风湿关节炎（RA）患者感受“寒湿”外邪后，常出现关节症状加重、疾病活动程度升高，但其机制尚不明确，研究外邪对人体的作用对RA防治有重要预防意义。肠道菌群在维持机体免疫平衡方面有重要作用，能通过调节Th/Treg平衡参与RA发病。我们从“肠道微生态”（环境-肠道菌群-宿主）失衡角度，推测寒湿外邪是通过引起RA宿主肠道菌群失衡，导致Th/Treg平衡改变来加重RA的。本课题拟应用动物实验，深入探讨寒湿外邪对RA病情的时间--强度量效关系，并通过动态观察寒湿外邪对大鼠肠道菌群多样性的影响，及关键微生物群变化与Th/Treg平衡关系，挖掘关键微生物群，最后通过粪便移植手段，进一步验证我们的推测。本项目是对中医“外感六淫致病”的理论运用现代微生物学、分子生物学方法的验证，能进一步揭示RA的发病机制及危险因素，对改善本病致畸致残的预后有重要意义。

类风湿关节炎（RA）患者在感受外感寒湿后会出现关节疼痛和炎症加重，但其发病机制尚不清楚。肠道菌群在维持免疫系统平衡方面起着重要作用，通过调节Th/Treg的平衡参与RA的发病。肠道菌群、环境和宿主构成了肠道微生态的动态平衡，推测外源性寒湿可引起肠道菌群失衡，导致Th/Treg平衡改变，加重RA的病情。本文研究了寒湿外感致病菌对肠道菌群多样性的影响以及Th/Treg平衡与关键菌群变化的关系。进一步揭示RA的发病机制和危险因素，对改善RA的预后具有重要意义。