目的观察穿山龙总皂苷对胶原诱导关节炎大鼠滑膜血管内皮生长因子、血管生成素2及其受体Tie-2的影响,探讨穿山龙总皂苷治疗类风湿关节炎的抗血管新生机制。方法建立胶原诱导关节炎大鼠模型,动物随机分为空白对照组、胶原诱导关节炎模型组、穿山龙总皂苷组、雷公藤多苷组(作为阳性对照组)和薯蓣皂苷元组,采用实时荧光定量PCR方法检测大鼠膝关节滑膜血管内皮生长因子mRNA的表达情况,采用免疫组织化学方法检测大鼠膝关节滑膜血管生成素-2及其受体Tie-2蛋白的表达。结果胶原诱导关节炎模型组大鼠滑膜血管内皮生长因子mRNA、血管生成素-2及Tie-2蛋白表达明显高于空白对照组(P〈0.01),经穿山龙总皂苷、雷公藤和薯蓣皂苷元治疗后血管内皮生长因子mRNA和血管生成素-2表达均低于胶原诱导关节炎模型组(P〈0.01);而Tie-2表达呈降低趋势,差异无统计学意义。穿山龙总皂苷组血管内皮生长因子mRNA表达比雷公藤组和薯蓣皂苷元组血管内皮生长因子mRNA明显降低(P〈0.01)。结论穿山龙总皂苷可能通过降低滑膜血管内皮生长因子mRNA、血管生成素-2及Tie-2的表达,抑制滑膜血管新生,从而对类风湿关节炎发挥治疗作用。
OBJECTIVE To study the effects of total saponin of Rhizoma Dioscreae Nipponicae (TSRDN) on the expression of vascular endothelial growth factor (VEGF), angiopoietin-2(Ang-2) and receptor Tie-2 in synovial tissue of collagen-induced arthritis (CIA) rats, and to investigate the antiangiogenesis mechanism of TSRDN in treating rheumatoid arthritis. METHODS After the CIA rat model was successfully established, the rats were randomly divided into 5 groups : normal control group, CIA model group, TSRDN group, tripterygium group, and diosgenin group. Real-time PCR was used to detect VEGF mRNA expression in synovial tissue of CIA rats, and immunohistochemical staining was used to observe angiopoietin-2 and receptor Tie-2. RESULTS VEGF mRNA, Ang-2 and Tie-2 expressions in synovial tissue of CIA rats were obviously higher than normal control group ( P 〈 0. 01 ). After treatment with TSRDN, tripterygium, and diosgenin, the expressions of VEGF mRNA and Ang-2 were obviously lower than those in CIA model group (P 〈 0. 01 ). But Tie-2 expression showed decreasing trend, and there was no obvious differences between each treatment group. VEGF mRNA expression in TSRDN group was much lower than that in tripterygium group and diosgenin group. CONCLUSION TSRDN can inhibit angiogenesis in synovial tissue by down regulating expressions of VEGF, Ang-2 and receptor Tie-2.