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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。
Objective: To study the effect and its mechanism of viper’s snake venom on angiogenesis in collagen-induced arthritis (CIA) rats. Methods: Rat CIA model was induced by bovine type Ⅱ collagen (1 g · L-1). After modeling for 21 days, the rats were divided into normal group, model group, meloxicam group (0.72 mg · kg-1, ig), low, medium and high dose group (0.1,0.33,1 mg · kg- 1, ip) once daily for 21 days. The synovial tissue of rats were scored by HE staining and the synovial microvessel density and the expression of vascular endothelial growth factor (VEGF) protein were detected by immunohistochemistry. The levels of Ang- 1) content. Results: Compared with the normal group, the ankle synovial pathological score and microvessel density of the model group were significantly increased (P <0.01), and the expression of VEGF and the content of serum Ang-1 in the synovial tissue were also significantly increased (P <0.01) Compared with the model group, the medium and high dose of viper snake venom significantly reduced the pathological score of ankle synovium of rats (P <0.05, P <0.01). The high dose of viper’s snake venom significantly reduced the microvessel density of the synovium, the expression of VEGF and serum Ang-1 content (P <0.05 or P <0.01). Conclusion: Snake venom can reduce joint pathological injury and angiogenesis in CIA rats. The mechanism may be related to the decrease of VEGF expression and the decrease of Ang-1 content.