中药薯蓣皂苷元对CIA大鼠滑膜组织VEGF及AP-Ⅰ表达的影响

Effects of Diosgenin on VEGF and AP-1 Expression in Synovial Tissues of CIA Rats

目的:通过观察中药薯蓣皂苷元对牛Ⅱ型胶原诱导型关节炎(Collagen-Induced Arthritis,CIA)大鼠膝关节滑膜激活蛋白-1(Activator Protein-1,AP-1),血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)的影响,探讨中药薯蓣皂苷元治疗类风湿关节炎的可能作用机制。方法:通过建立大鼠CIA模型,实验随机分空白对照组、CIA模型组、中药薯蓣皂苷元组和阳性药物对照组(雷公藤多苷组),采用原位杂交方法检测膝关节滑膜组织AP-1(c-fos和c-jun)的表达情况,应用Real-Time PCR方法检测大鼠膝关节滑膜组织VEGF m RNA的表达情况。结果:CIA模型组大鼠膝关节滑膜组织c-jun、c-fos和VEGF mRNA表达明显高于空白对照组;应用中药薯蓣皂苷元及雷公藤治疗后,c-jun、c-fos和VEGF m RNA表达明显降低。结论:薯蓣皂苷元可能通过对AP-1的两个亚单位c-jun和c-fos的调节来影响滑膜组织VEGF的表达,进而抑制滑膜血管新生,从而对类风湿关节炎发挥治疗作用。

This paper was aimed to study effects of diosgenin on expressions of activator protein-1（AP-1） and vascular endothelial growth factor（VEGF） in synovial tissues of collagen-induced arthritis（CIA） rats induced by bovine type II collagen, in order to investigate the possible mechanism of herbal medicine diosgenin in the treatment of rheumatoid arthritis（RA）. After the CIA rats models were successfully established, rats were randomly divided into the blank control group, CIA model group, diosgenin group, and positive medicine control（tripterygium） group. The in situ hybridization was used to detect the expressions of AP-1（c-fos and c-jun） in synovial tissues of the knee joint. The real-time PCR was used to detect the VEGF m RNA expression in synovial tissues of rats＇ knee joints. The results showed that c-jun and c-fos, VEGF m RNA expressions in synovial tissues of rats＇ knee joints were obviously higher than that of the blank control group（P〈0.01）. After treatment of diosgenin and tripterygium, the expressions of c-jun and c-fos, VEGF m RNA were significantly reduced（P〈0.01）. It was concluded that diosgenin may regulate the expression of VEGF in synovial tissues through c-jun and c-fos of AP-1 in order to inhibit synovial angiogenesis for the treatment of RA.