蕲蛇蛇毒对胶原诱导性关节炎大鼠血管生成的影响

目的： 研究蕲蛇蛇毒对胶原诱导性关节炎（CIA）大鼠血管生成的影响及其机制。 方法： 采用牛Ⅱ型胶原（1 g·L^-1）诱导大鼠CIA模型。建模21 d后，实验分正常组、模型组、美洛昔康组（0.72 mg·kg^-1， ig）、蕲蛇蛇毒低、中、高剂量组（0.1， 0.33， 1 mg·kg^-1， ip），每天1次，连续治疗21 d。采用HE染色对大鼠踝关节滑膜组织进行病理学评分，免疫组化法检测滑膜微血管密度和血管内皮细胞生长因子（VEGF）的蛋白表达，ELISA法检测血清中血管生成素1（Ang-1）的含量。 结果： 与正常组比较，模型组大鼠踝关节滑膜病理评分和微血管密度显著增加（P<0.01），滑膜组织VEGF表达量及血清Ang-1含量亦显著增加（P<0.01）；与模型组比较，蕲蛇蛇毒中、高剂量能显著降低大鼠踝关节滑膜的病理评分（P<0.05，P<0.01），蕲蛇蛇毒高剂量能明显降低滑膜微血管密度、VEGF表达和血清Ang-1含量（P<0.05或P<0.01）。 结论： 蛇毒能减轻CIA大鼠的关节病理损伤和血管新生，其机制可能与降低VEGF表达和减少Ang-1含量有关。

Effect of Agkistrodon acutus Venom on Angiogenesis in Rats with Collagen-induced Arthritis

Objective: To explore the effect of Agkistrodon acutus venom on angiogenesis in collagen-induced arthritis (CIA) rats. Method: CIA was induced in Lewis rats with bovine type II collagen (1 g·L^-1). After induction of CIA for 21 d, rats were randomly divided into six groups:normal group, CIA model group, meloxicam group (0.72 mg·kg^-1,ig), A. acutus venom groups (0.1, 0.33, 1 mg·kg^-1,ip). After treatment once a day for 21 d.The histopathological score was monitored by HE staining in ankle joint synovial tissues, and the microvessel density (MVD) was detected by Von Willebrand factor (vWF) immunostaining. Vascular endothelia growth factor(VEGF) expression and the serum level of angiopoientin 1(Ang-1) were examined by immunohistochemistry and ELISA respectively. Result: Compared with the normal group, histopathological score and MVD significantly increased in CIA model group, as well as the VEGF expression and the serum level of Ang-1 (P<0.01). Compared with CIA model group, histopathological score was significantly decreased by treatment with medium and high dose of A. acutus venom (P<0.05 or P<0.01). Moreover,the MVD, the VEGF expression and the serum level of Ang-1 were significantly reduced by high dose of A. acutus venom( P<0.01). Conclusion: These results suggest that A. acutus venom effectively alleviate the pathological damage and angiogenesis, and its mechanism might be partly related to the decreasing expression of VEGF in ankle joint synovial tissues and the content of Ang-1 in serum.