电针干预RA大鼠血管翳形成的HIF-1α/MDM2/p53信号通路调控机制

血管翳形成是类风湿关节炎（RA）病情进展的特征性标志，极易导致患者出现骨破坏和残疾，是目前RA研究的热点问题。电针治疗可以有效的控制RA的病情进展，安全性好，其作用机制仍待进一步研究。课题组前期研究证实电针足三里、悬钟穴可以有效的抑制血管翳形成；而HIF-1α/MDM2/p53信号在血管翳形成中发挥着关键作用。因而我们提出假设：电针可能通过调控增殖的滑膜细胞内分泌的HIF-1α的表达，作用于MDM2/p53信号途径，抑制血管翳的形成。本课题在前期研究基础之上，拟以活血通络为基本治法，综合运用组织病理、免疫组化、PCR、Western blot等分子生物学检测电针对RA模型血管翳形成、滑膜细胞增殖以及HIF-1α/MDM2/p53信号通路的影响，阐明电针干预血管翳形成的调控机制，揭示电针治疗RA的新的途径，为针灸治疗RA提供新的研究依据。

Angiogenesis is the typically pathogenesis sign of rheumatoid arthritis,which easily lead to bone destruction and disability in patients,also is the current clinical hot issues in RA. Electroacupuncture treatment can effectively control the progress of RA disease with little side effect, while the mechanism of treatment remains to be further studied.The preliminary study of our researches confirmed that electroacupuncture at Zusanli, xuanzhong acupoints can effectively inhibit the angiogenesis. Recent studies have shown that the HIF-1α / MDM2 / p53 signaling pathway plays an important role in the angiogenesis, which is the focus of current research.Therefore, we hypothesized that electroacupuncture treatment may inhibit the formation of angiogenesis by modulating the over expression of HIF-1α in synovial cells and acting on the MDM2 / p53 signaling pathway. In this study, the “activating blood and collaterals” will be the basic principle, the histopathology, immunohistochemistry, PCR, Western blot and other molecular biology will be used to detect the effect of electroacupuncture on the angiogenesis, synovial cell proliferation and HIF-1α / MDM2 / p53 signaling pathway in RA model. To confirm the effect mechanism of electroacupuncture on the angiogenesis, and to provide a new experimental basis for acupuncture treatment of RA.