金雀异黄素协同雷公藤多苷治疗去卵巢大鼠类风湿关节炎的药效学研究

Study on Pharmacodynamics of Genistein Combined with Tripterygium Glycosides on Rheumatoid Arthritis Treatment of Ovariectomized Rats

目的:观察金雀异黄素协同雷公藤多苷治疗去卵巢大鼠类风湿关节炎的疗效。方法:将SD大鼠随机分为4组:假手术组、模型组、甲氨喋呤治疗组和金雀异黄素协同雷公藤多苷治疗组(10只/组)。除假手术组外,其余大鼠均行卵巢摘除术并于尾根注射II型胶原诱导关节炎大鼠模型(CIA)。甲氨喋呤(2.7 mg·kg-1)、雷公藤多苷(70 mg·kg-1)及金雀异黄素(30 mg·kg-1)灌胃给药(1次/天,连续2周)。通过测量大鼠关节炎指数、关节肿胀度和血清中Col II抗体、IL-6及IL-10水平评价疗效。结果:模型组大鼠关节炎指数、关节肿胀度及血清中Col II抗体、IL-6及IL-10水平均显著增高(P<0.05或P<0.01);与模型组比较,甲氨喋呤和金雀异黄素协同雷公藤多苷治疗组大鼠关节炎指数及关节肿胀度均显著下降(P<0.01),甲氨喋呤治疗组大鼠血清中Col II抗体水平明显降低(P<0.05),而IL-6和IL-10水平没有显著改变。与之对应,金雀异黄素协同雷公藤多苷治疗组大鼠血清中Col II抗体及IL-6水平明显降低(P<0.05),IL-10水平显著增高(P<0.01)。结论:金雀异黄素协同雷公藤多苷可显著抑制去卵巢大鼠CIA的发生和发展,且对IL-6、IL-10的调节作用优于甲氨喋呤,提示植物雌激素协同雷公藤制剂对性腺功能异常型RA具有较好的治疗作用,为临床女性绝经后RA的治疗提供了新思路和实验依据。

This study was aimed to observe the pharmacodynamics of genistein combined with tripterygium gly-cosides （ GTW ） in the rheumatoid arthritis （ RA ） treatment of ovariectomized rats . SD rats were randomly divid-ed into four groups , which were the sham-operation group , model group , Methotrexate （ MTX ） treatment group （ 2.7 mg/kg ） , and genistein （ 30 mg/kg ） combined with GTW （ 70 mg/kg ） treatment group . There were ten rats in each group . Except the sham-operation group , rats in other groups were ovariectomized and immunized by collagen type II to prepare collagen induced arthritis （ CIA ） model . The intragastric administration of drugs was given once a day for two weeks . The arthritis index , joints swelling degree , and levels of anti-Col II , IL-6 and IL-10 in serum were tested . The results showed that the arthritis index , joints swelling degree , and levels of anti-Col II , IL-6 and IL-10 in serum were all significantly increased in the model group （ P 〈 0 . 05 or P〈 0 . 01 ） . Compared with the model group , the arthritis index and joints swelling degree of both MTX and genistein combined with GTW were significantly decreased . The level of anti-Col II in serum of the MTX treatment group was significantly decreased （ P 〈 0 . 05 ） . However , there were no significant changes on levels of IL-6 and IL-10 . The levels of anti-Col II and IL-6 in serum of the genistein combined with GTW were significantly decreased （ P 〈 0 . 05 ） . The level of IL-10 was significantly increased （ P 〈 0 . 01 ） . It was conclud-ed that genistein combined with GTW can significantly inhibit the pathological progress of CIA on ovariec-tomized rats . Compared with MTX , the genistein combined with GTW received a better regulating effect on the expression of IL-6 and IL-10 . The results suggested that phytoestrogen combined with GTW played a good therapeutic effect on gonadal dysfunction type of RA . It provided novel strategies and experimental evidences on postmenopausal RA treatment in the clinical practice .