蜂毒对Ⅱ型胶原诱导的关节炎大鼠滑膜血管生成的影响

One of the main pathological changes of Rheumatoid Arthritis is the formation of synovial pannus, and the cartilage and bone tissues are eroded, which cause the destruction of joint structures and failure of functions. Bee therapy has been accepted and paid more attention to by more and more doctors and RA patients because of its nice effects, which its mechanism of action is still unknown. There are evidences that angiogenesis has an important role during the development of RA. It can form synovial pannus that affect the joints functions. The hyperplasia of synovial pannus is tumor-like in the joint synovium, therefore, the genesis mechanism of theformation of synovial pannus may be similar to the angiogenesis of tumor. Currently, the clinical tests of the application of Vascular Endothelial Cell Growth Factor (VEGF) antibody and receptor tyrosine kinase small molecular inhibitors among patients with tumors have already been doing. It is predictable that VEGF targeted treatment may be selectively used to RA. In this study, the origin of cell of the proliferated vessels in synovial pannus was determined first by the observation of synovium pathological sections of the knee joints of rats after bone marrow transplantation. The animal models of Collagen Ⅱ-induced Arthritis (CIA), which is similar to RA of human beings, was established to study the effect of bee venom on the synovium angiogenesis of rats with CIA, so as to reveal the functional mechanism of bee venom in dealing with RA, and provide theoretical and experimental basis for the treatment of RA by bee venom therapy.

类风湿性关节炎（RA）的主要病理改变之一为滑膜翳形成，软骨及骨组织侵蚀，最终导致关节结构破坏，功能丧失。蜂针疗法以其良好的疗效受到医生与广大RA患者的肯定和重视，但其作用机制尚未明了。研究表明，血管生成在RA病变过程中发挥了重要作用，它可以形成滑膜翳，影响关节功能。关节滑膜中血管翳呈肿瘤样增生，因此，滑膜翳的形成可能与肿瘤血管形成有相似发生机制，目前在肿瘤患者中使用血管内皮细胞生长因子（VEGF）抗体和受体酪氨酸激酶小分子抑制剂的临床试验已在进行中，可以预见，VEGF靶向治疗也可能会选择性地用于RA。本课题首先通过观察骨髓移植后大鼠膝关节滑膜病理切片，确定滑膜翳增生血管的细胞起源，并建立与人体类风湿性关节炎相似的Ⅱ型胶原诱导的关节炎(CIA)动物模型，研究蜂毒对CIA大鼠滑膜血管生成的影响，揭示蜂毒治疗RA的作用机制，为蜂毒疗法治疗RA提供理论和实验依据。

蜂针疗法在临床治疗类风湿性关节炎的观察中已取得医生与患者的广泛认可和良好的疗效，但针对其作用机制的研究仍在进行中。本项目聚焦于类风湿性关节炎的典型病理改变——关节滑膜增生，展开一系列相关的实验。从与人类类风湿性关节炎相似的CIA动物模型入手，通过在SD大鼠与Wistar大鼠的造模对照，寻找更为稳定、成模率较高、较为经济的造模对象。在成功复制CIA模型的基础上，以临床公认、疗效确切的甲氨蝶呤和TNF-α拮抗剂依那西普作为对照组，观察蜂针蜂毒对CIA大鼠的治疗作用。与模型对照组比较，蜂毒组、甲氨蝶呤组、TNF-α拮抗剂组的关节炎评分均有下降趋势，蜂毒亦可改善CIA模型大鼠的膝关节病变，但改善程度不及甲氨蝶呤组和TNF-α拮抗剂依那西普组，可能与蜂毒剂量不足或治疗周期较短有关，但这一实验结果显示出蜂毒在治疗时间较短、用量较少的情况下仍然具有改善CIA大鼠关节炎症的作用趋势，为未来的更进一步研究打下了客观、可行的基础。