甲氨蝶呤（MTX）是治疗类风湿关节炎（RA）的常用药，目前认为上调腺苷及受体A2A（A2AAR）是其发挥抗炎作用的重要机制。MTX疗效只有46%-65%，一直来认为与MTX作用和代谢的基因多态性有关，但A2AAR偶联信号变化对MTX作用的影响未见报道。A2AAR属G蛋白偶联受体（GPCRs），β-arrestin2是大部分GPCRs的负调节因子，在细胞增殖分化调控中十分重要。本课题拟在以往工作基础上，观察胶原性关节炎大鼠病程不同阶段以及MTX治疗有效或无效时体内腺苷水平、滑膜细胞β-arrestin2和A2AAR信号的变化规律，采用流式细胞术、激光共聚焦等技术，利用A2AAR激动剂（CGS-21680）和小干扰RNA等工具，观察β-arrestin2对A2AAR信号的调节特点及在MTX抑制滑膜细胞异常增殖中的作用。为进一步阐明RA发生机制、病程变化特点和药物合理治疗提供理论依据。

Methotrexate (MTX) is widely used in treating rheumatoid arthritis (RA) principally via up-regulating adenosine and its receptor A2A (A2AAR) as was revealed in recent years. However, the ACR20 response rate to MTX treatment is between 46%-65% which is considered to associate with the polymorphisms of targets and metabolic enzymes of MTX, but there is no firm evidence shows whether signaling mediated by A2AAR can influence the efficacy of MTX. A2AAR belongs to the G protein coupled receptors (GPCRs) family. β-arrestin2 is an important negative regulator for most GPCRs, and plays a key role in controlling cell proliferation and differentiation. This study will detect the changes of serum and joint adenosine, β-arrestin2 expression and A2AAR signaling in synoviocytes in different disease processes of collagen induced arthritis (CIA) rats and in MTX treating CIA rats. In addition, we will illuminate the characteristics of β-arrestin2 in regulating A2AAR signaling and its effect on MTX efficiency in attenuating synoviocytes hyperplasia by using A2AAR selective agonist CGS-21680, small interfering RNA, and applying advanced techniques for instance flow cytometry, laser scanning confocal microscope, etc. This work should improve our understanding of the pathogenesis of RA and promote rational MTX therapy.