清热活血方是名医路志正教授治疗活动期类风湿关节炎(RA)的经验方，临床疗效肯定，可改善患者关节肿痛、缩短晨僵时间、延缓骨破坏。前期研究表明，该方通过调控炎性因子和血管生成相关因子的表达，发挥抑制滑膜炎症、血管新生和骨破坏的作用。RA病因学最新研究发现肠道致病菌的过度生长和免疫调节性共生菌的缺乏可能导致关节慢性炎症的发生，且DMARDs治疗可改善肠道菌群失衡。由此推测，清热活血法疗效的可能机制之一是通过调控肠道微生态失衡，调节Th/Treg平衡及炎症因子表达，发挥治疗活动期RA的效果。本研究拟采用宏基因组测序与分析、PCR-DGGE分析、Western blot、micro-CT等前沿技术，人体试验与动物实验相结合，从整体-细胞-分子层面验证假说的客观性，以调节肠道微生态和免疫平衡角度揭示清热活血法治疗活动期RA的分子机制，对传承和挖掘名老中医经验、阐释其理论的科学内涵和RA防治提供新思路。

Qingre Huoxue Decoction(QRHXD) is an empiric therapy of the famous TCM doctor for treating RA. It has been proved having a reliable clinical effect by relieving pain, shortening morning stiffness time and prolonging bone destruction. Previous researches showed that QRHXD could inhibit synovitis, angiogenesis and bone erosion through modulating expressions of inflammatory cytokines and angiogenic factors. The latest study showed that RA represents a state of chronic inflammation that might be provoked or aggravated by the overgrowth of pathogenic bacteria or a lack of immune-modulating commensal bacteria, which could be treated by DMARDs. Based on above, we speculate that one of the possible mechanisms of QRHXD on treating RA is regulating dysbiosis of intestinal microecology to balance Th/Treg immunity and inhibit the expression of pro-inflammatory cytokines. In this project, we combine human and animal models to explore the treating mechanism of QRHXD from body-cell-molecule stages by advanced methods such as Metagenomics, PCR-DGGE, Western blot, micro-CT, etc. , which is of great significance to inherit the famous TCM doctor's experience, reveal its scientific connotation, and provide new ideas for treating RA as well.