类风湿关节炎(RA)是一种慢性自身免疫性疾病，近年研究显示JAK2/STAT3通路介导的Th17/Treg失衡在RA发病中起关键作用。桂枝芍药知母汤是有效治疗RA的经典名方，祛风除湿、温经散寒为其主要功效。我们前期研究发现：桂枝芍药知母汤可下调RA患者CD4+T细胞中Th17/Treg比例，并可抑制JAK2蛋白磷酸化。因此提出科学假说：该方通过JAK2/STAT3通路抑制CD4+T细胞向Th17分化及其异常功能活化，促进Treg分化及其相关细胞因子分泌，以调控Th17/Treg平衡，纠正RA免疫紊乱状态以发挥治疗作用。本项目拟通过RA患者CD4+T细胞体外模型和RA小鼠体内模型，应用RNA干扰、慢病毒转染、流式细胞术等方法，探讨该方通过JAK2/STAT3通路调控Th17/Treg平衡的作用机制，揭示该方有效治疗RA的作用机理和靶点，为祛风除湿、温经散寒法治疗RA提供现代分子生物学依据。

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and recent studies have shown that JAK2/STAT3 signaling pathway-mediated Th17/Treg imbalance play a key role in the pathogenesis of RA. Guizhi Shaoyao Zhimu Decoction(GSZMD) is a classic prescription for the effective treatment of RA, and the method of eliminating wind and dampness and warming channel for dispelling cold is its main effects. Our previous study found that GSZMD can reduce the ratio of Th17/Treg in CD4+T cells of RA patients, and inhibit the phosphorylation of JAK2 protein. Therefore, we propose a scientific hypothesis: GSZMD inhibits the differentiation of CD4+T cells into Th17 and its abnormal function and promotes Treg differentiation and related cytokine secretion, regulates Th17/Treg cell balance through JAK2/STAT3 signaling pathway, thus corrects immune disorder to play a therapeutic role in RA. This project intends to use the in vitro model of CD4+T cells of RA patients and the in vivo model of RA, using some technologies such as RNA interference, lentiviral transfection and flow cytometry, to study the effect of GSZMD on Th17/Treg cell balance via JAK2/STAT3 signaling pathway. This reveals the mechanism and target of effective treatment of RA with GSZMD, and provide modern molecular biological basis for the method of eliminating wind and dampness and warming channel for dispelling cold for RA.