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当归拈痛汤对类风湿性关节炎作用机理及配伍的实验研究
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摘要
类风湿性关节炎(RA)是当前世界范围内严重威胁公众健康的慢性疾病之一。其病因繁多,发病机制复杂。当归拈痛汤是临床治疗RA的有效方剂。本课题以当归拈痛汤为研究对象,以RA为研究切入点,对该方抗炎免疫作用及治疗RA的作用机理进行了较为深入的研究。并将该方进行了拆方配伍研究,探讨了蠲痹法和扶正法在当归拈痛汤中的配伍意义。
     目的:研究当归拈痛汤对RA的作用机理及配伍意义。
     方法:以佐剂性关节炎大鼠(AA)作为实验模型,以雷公藤多甙片为阳性对照药,进行拆方研究(分为当归拈痛汤全方组、蠲痹组、扶正组),观察大鼠足跖肿胀度、压力耐痛值、胸腺、脾脏指数,以及关节内病理组织学变化;通过对血清相关炎性细胞因子、红细胞天然免疫指标的检测和滑膜组织相关的粘附因子、血管内皮生长因子、基质金属蛋白酶、凋亡因子Fas/FasL mRNA表达,探讨了当归拈痛汤及其各个拆方组对AA大鼠的抗炎及免疫调节作用以及部分机理。
     结果:(1)当归拈痛汤有明显的抗炎、镇痛、免疫调节作用,可显著抑制AA大鼠足跖肿胀及多发性关节炎,提高AA大鼠的压力耐痛值,改善AA大鼠的免疫器官指数,同时明显减轻病变关节滑膜炎症与增生、防止关节软骨及骨质的破坏。(2)当归拈痛汤通过抑制AA大鼠过高的炎性细胞因子TNF-a、IL-1分泌、提高大鼠红细胞天然免疫功能,而发挥抗炎和免疫调节作用。(3)在病变关节滑膜局部,当归拈痛汤能抑制AA大鼠滑膜细胞异常增高的ICAM-1的表达,从而抑制滑膜的炎症与增殖。(4)当归拈痛汤能下调滑膜组织中VEGF表达,减少血管新生,由此抑制血管翳的形成。(5)当归拈痛汤还可下调滑膜组织中MMP-3表达,防止软骨和软骨下骨的侵蚀。(6)当归拈痛汤可以促进凋亡因子Fas/FasL mRNA表达,改善AA大鼠的滑膜细胞凋亡障碍。
     结论:当归拈痛汤具有多层次、多途径、多靶点的抗炎及免疫调节作用。当归拈痛汤的抗炎、免疫调节作用与其抑制炎性细
Rheumatoid arthritis (RA) is one of serious chronic diseases which threat public healthy in the world, the mechanism of outbreak is complicated. Dangguiniantong tang had a good effect to treat RA. This reseach carry on a deep study on anti-inflammation, immunity and treatment mechanism to RA of Dangguiniantong tang. By the decomposition and compatibility study, explored the meaning of juanbi method and fuzheng method in Dangguiniantong tang.Objective: study the mechanism of Dangguiniantong tang treat RA and the meaning of compatibility.Methods: take adjuvant induced arthritis rat as experiment model, treat with Dangguiniantong tang, each decomposition and TriPterygium Glycosides in different groups. Observe the swelling of arthritis, press-risisting index, thymus, spleen index , pathology change in arthritis, and the express of CK, ICAM-1, IL-1, VEGF, MMP, Fas/FasL mRNA, explore the anti-inflammation, immunity and partial treatment mechanism to RA of Dangguiniantong tang and it's decomposition.Results: (1)Dangguiniantong tang has obviously effect of anti-inflammation, inhibition swelling of arthritis, increase the perss-resisting index, it can also lighten the synovial inflammation and hyperplasia of lesion joints distinctly, and prevent the joint cartilage and bone from destruction. (2)Dangguiniantong tang can retain the excessive decimrter of TNF- a、 IL-1, improve the immunity function of RBC, so as to give play to anti-inflammation and immunity adjust. Juanbi method has good effect on anti-inflammation and fuzheng method has good effect at immunity adjust. (3) in locat joints, Dangguiniantong tang can retain the excessive express of ICAM-1, thus retain the inflammation and
    proliferation of synovial tissue. (4).Dangguiniantong tang can decrease the express of VEGF in synovial tissue, drcrease the growth of new vessel, retain the form of pannus. (5) Dangguiniantong tang can decrease the express of MMP-3 in synocial tissue, prevent the destroy of bone and cartilage. (6) Dangguiniantong tang can increase the express of Fas/FasL mRNA, improve the disorder of PDD.Conclusions: Dangguiniantong tang has the effect of anti-inflammation and immunity adjust, they are related with inhibite expression of inflammation CK and improve the immunity function of RBC. By the way of adjusting the express of MMP-3, Fas/FasL mRNA, VEGF, ICAM-1 in synocial tissue, Dangguiniantong tang control the inflammation of synocial, and prevent the distory of bone and cartilage. Juanbi method has good effect at anti-inflammation, and fuzheng method has good effect at immunity adjust, they have good compatibility effect in whole prescribe.
引文
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