雷公藤甲素对胶原诱导关节炎大鼠滑膜血管新生的调节作用

Regulatory effect of triptolide on angiogenesis in synovium of collagen-induced arthritis rats

目的观察雷公藤甲素（TP）对血管新生的影响，探讨TP治疗关节炎的作用机制。方法建立胶原诱导关节炎（CIA）大鼠模型，常规苏木素-伊红（HE）染色，测量关节体积，计算关节炎指数和病理积分，分别检测滑膜和血清中血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和内皮抑素（endostatin）的蛋白表达，并通过CD34给滑膜血管密度计数（MVD）。结果CIA大鼠滑膜和血清中VEGF、bFGF及滑膜MVD明显高于正常组（x^2分别为65．3、31．6，q=9．2，三者P〈0．01），endostatin的表达与正常组差异无统计学意义（x^2=0．8，P〉0．05）。TP治疗后，滑膜和血清中VEGF、bFGF、滑膜MVD均下降（x^2分别为19．7、6．0，q=6，5，三者P〈0．01），而endostatin表达却升高（x^2=3．9，P〈0．05），甲氨蝶呤（MTX）则主要以endostatin表达升高为主（x^2=17．9，P〈0．01）。结论生长因子的表达失衡可能在关节炎的形成及发展过程中起重要作用，TP能够调整生长因子的失衡状态而发挥治疗作用。

Objective To study the regulatory effect of triptolide （TP） on the angiogenesis of collagen-induced arthritis （CIA） rats. The effect of TP on arthritis is also explored. Methods After the model of CIA was established, the articular volume was measured and the synovium was examined with regular HE stain and the inflammation and pathological changes were evaluated. In addition, the vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF） and endostatin protein expressions in synovium and serum were tested. The micro-vessel density （MVD） of synovium was also measured by caulating CD34 level. Results The expressions of VEGF, bFGF and MVD in CIA rats＇ synovium and serum were evidently higher than the control group （x^2=65.3, 31.6, q=9.2, P〈0.01, respectively）, while the expression of endostatin showed no statistical difference with controls （X^2=0.8, P〉0.05）. After treated with TP, the expressions of VEGF, bFGFand MVD decreased markedly （x^2=19.7, 6.0, q=6.5, P〈0.01, respectively）, but the protein expression of endostatin significantly increased （X^2=3.9, P〈0.05）. However, only the expression of endostatin increased significantly after treated with MTX （X^2=17.9, P〈0.01 ）. Conclusion Imbalance in growth factors production may play an important role in the process of arthritis development. Re-establishing the balance of growth factors maybe one of the mechanisms of TP in the treatment of arthritis.