血管紧张素Ⅱ（AngⅡ）及受体参与炎症免疫调节。阻断AngⅡ1型受体（AT1R）缓解类风湿关节炎（RA）及动物模型炎症免疫反应，改善滑膜细胞活化、功能。AngⅡ2型受体（AT2R）及信号转导可拮抗AT1R功能。课题组发现，AT2R激动剂缓解滑膜炎，AT1R/AT2R失平衡促进RA进展。本项目利用大鼠胶原性关节炎（CIA）和RA患者巨噬细胞样滑膜细胞（MLS），采用激光共聚焦、免疫共沉淀、电泳迁移实验、基因表达谱芯片、siRNA及AT2R、AT1R药理学工具，研究RA的MLS活化、功能变化；探讨AT2R、AT1R信号转导及与MAPKs交叉对话在MLS活化、功能变化的作用；利用AT1R或AT2R敲除小鼠制备CIA模型，研究AT2R、AT1R信号对CIA的MLS活化、功能的影响。为揭示AngⅡ及受体信号对RA异常活化MLS的调节作用以及发现AT2R作为RA滑膜炎治疗靶点提供实验依据。

Angiotensin Ⅱ(AngⅡ) and receptors participate in the modulation of inflamation and immunity. Ang Ⅱ type 1 receptor (AT1R) blocker ameliorates the rheumatoid arthritis (RA) and experimental models progression, and improves the synoviocytes dysfunction and activation. Ang Ⅱtype 2 receptor (AT2R) mainly exerts counter-regulatory actions to AT1R. Our previous study indicated that AT2R agonist alleviated the synovitis, and AT1R/AT2R imbanlance promoted RA development. Based on rat collagen induced arthritis (CIA) and RA macrophage-like synoviocyte (MLS), the change of MLS dysfunction and activation, as well as the role of Ang Ⅱ receptors signaling and MAPKs cross-talk, were studied using the the laser confocal microscopy, electrophoretic mobility shift assay,co-immunoprecipitation,siRNA, and Ang Ⅱ receptors pharmacology tools. Also, the fluence of Ang Ⅱ receptors signaling on MLS dysfunction and activation was studied using AT1R or AT2R knock-out mouse. The designed work will illustrate the role of Ang Ⅱ receptors signaling on MLS activation, and provide evidence for AT2R for treating RA as novel target.