类风湿关节炎（RA）是一种慢性、炎症性、系统免疫疾病。RA可能通过改变受成纤维滑膜细胞(FLS)表达的肌动蛋白（F-actin）调控的血-关节囊液屏障（BJB）的结构和状态，改变通透性、清除率和代谢之间的平衡，大量有害物质在关节腔中聚集，加重病情。RA患者的滑膜液和外周血的多种细胞中，存在MicroRNA (miRs)的异常调节。miRs有望成为 RA 新的诊断标志物和治疗靶点。建立大鼠佐剂性关节炎(AA)和胶原性关节炎(CIA)模型，采用整体给药和体外细胞培养实验手段，多位点微透析技术在线同步研究药动-药效结合作用；应用病理形态学、流式细胞术、免疫荧光染色、实时PCR和蛋白免疫印迹技术，以AA和CIA大鼠FLS中miR146a和miR124a这一对相反变化趋势的miRs为突破口，探讨牛膝引药下行，FLS表达F-actin水平的改变、BJB对栀子苷（GE）通透性的影响，揭示中药引经理论的科学内涵，探究GE对G蛋白偶联受体和整合素受体-MAPKs-miR146a/124a-F-actin调号调节的影响，为构建筛选治疗RA新的药物作用靶点提供技术平台，为中药有效成分研究与应用提供实验依据。

Rheumatoid arthritis (RA) is a chronic, inflammatory and systemic autoimmune disease. RA may change the structure and state of blood-joint barrier (BJB) regulated by filamentous actin (F-actin) in fibroblast-like cells synoviocytes (FLS), so as to change its permeability. MicroRNA (miRs) is expected to become the new diagnostic markers and therapeutic targets for RA. Adjuvant arthritis (AA) model of rat is established in the research. Using the treatment of Geniposide (GE) and cells culture in vitro experiments, sites-microdialysis (sites-MD) technique; studying the interaction of pharmacokinetic and pharmacodynamic (PK-PD) online synchronization; applying pathomorphology, flow cytometry, immunofluorescence staining, real-time PCR and Western blot, we investigate the "drug-guide" effect of achyranthes bidentata, the level of F-actin in FLS, the effect of BJB on the permeability of GE, and the role of GE in G-protein coupled receptors and integrin receptors-MAPKs-miRs-F-actin signalling pathway, thereby further revealing the pathological mechanism of RA, exploring the scientific connotation of traditional Chinese medicinal guide, studying in-depth the effect of GE on therapeutic mechanism of RA, and providing a technical platform for screening new drug targets for the treatment of RA.