从调节Th17/Treg失衡探讨祛风通络活血法对风寒湿痹关节炎的作用机制

Rheumatoid arthritis (RA) is a common systemic disorder characterized by autoimmunity and chronic in?ammation of multiple joints. Collagen-induced arthritis (CIA) is a well-established animal model of RA. Although the mechanisms is unknown, recent studies have suggested that highly proin?ammatory IL-17-producing Th17 cells,rather than Th1 cells, are central to the pathology of autoimmune arthritis IL-17-producing CD4+ T cells contribute to severe synovitis, pannus formation, joint destruction in arthritis joints and autoimmune in?amma- tion. On the other hand, there is ample evidence that CD4+/CD25+/Foxp3+ regulatory T (Treg) cells also play a critical role on the inhibition of autoimmune reaction.So the hot research areas of RA is imbalance of Th17/Treg.The main cause of traditional Chinese medicine thinks RA is deficiency disease of spleen-liver-kidney, cold and dampness phlegm and blood stasis standard for disease.Qufeng tongluo huoxue method is the principle of treatment wind-cold-dampness arthralgia arthritis. Jitongning capsule is the clinical experience prescription, benefit is qufeng tongluo huoxue to prescription pain law.The experimental results showed that Jitongning capsule had significant effect to stimulating collagen rat arthritis , not only can reduce joint swelling degree, and have inhibit the expression of inflammatory factor IL-17 which secreted by Th17 . This study point is observe the imbalance Th17 / Treg cells in arthritis, discusses impossible mechanism of qufeng tongluo huoxue method for wind-cold-dampness arthralgia arthritis.

类风湿关节炎 (RA) 是一种慢性进行性的自身免疫性疾病。其病因及发病机制目前尚不明确，近年来研究显示随着疾病活动性的增加 RA 患者外周血 CD4+T 细胞中Th17细胞的比率增加，而调节T细胞 （Treg）的比率降低，导致 Th17 /Treg 细胞的比例失衡，因此Th17 /Treg 细胞的比例失衡是近期RA发病机制研究的热点。中医认为RA的主要病因病机为肝脾肾气血亏虚，风寒湿热痰瘀入侵而发病。祛风通络活血是临床用于治疗风寒湿痹证的常用治则。祛风通络活血药物脊痛宁胶囊是我们临床经验总结的处方。既往的实验研究结果显示脊痛宁胶囊对胶原诱导性大鼠关节炎有显著的抑制作用，不但可以减轻关节肿胀程度，而且对血清中Th17分泌的细胞因子IL-17有明显的抑制作用。本研究拟从探讨祛风通络活血法对风寒湿痹关节炎大鼠Th17/Treg细胞的失衡的角度，探讨祛风通络活血法对风寒湿痹关节炎的作用机制

本课题成功建立了类风湿关节炎风寒湿痹大鼠模型，确证脊痛宁胶囊对风寒湿痹型类风湿关节炎大鼠的治疗作用，研究发现脊痛宁胶囊对风寒湿痹型类风湿关节炎大鼠炎症细胞因子的抑制作用；同时证实脊痛宁胶囊对风寒湿痹型类风湿关节炎大鼠骨破坏抑制作用，明确脊痛宁胶囊对风寒湿痹型类风湿关节炎大鼠Th17/Treg细胞失衡的调节作用，观察脊痛宁胶囊对风寒湿痹型类风湿关节炎大鼠滑膜组织JAK/STAT信号通路的调控机制。脊痛宁胶囊含药血清有抑制成纤维细胞样滑膜细胞增殖的作用，并可下调 TNFα、IL-6、及IL-17 mRNA的表达，上调IL-10mRNA及TGFβmRNA的表达。研究结果明确了祛风通络活血法（脊痛宁）对类风湿关节炎发病中占用重要地位的Th17/Treg失衡的调节作用。