青藤碱对胶原诱导型关节炎免疫抑制作用的机制研究

为证实青藤碱(SINO)抗关节破坏的作用,揭示其可能的作用途径,采用牛II型胶原混合弗氏不完全佐剂于Wistar大鼠尾根部注射。足肿后随机分为造模加生理盐水组、造模加雷公藤多苷(TG)治疗组和造模加SINO治疗组,容积法每天测量后肢肿胀度。给药后第35天,乳腺钼靶机大鼠全身摄片,计分法评价四肢关节骨侵蚀和关节间隙变化;取足趾关节和腹股沟淋巴结,HE染色,评价病理情况;培养原代滑膜细胞,放免法检测培养上清IL-6,RT-PCR检测IL-6 mRNA表达。结果显示,SINO和TG可明显抑制关节肿胀,骨侵蚀和关节间隙变化(P<0.01);抑制CIA大鼠滑膜增生、软骨破坏、淋巴结生发中心反应和髓索浆细胞浸润(P<0.01);降低滑膜细胞IL-6 mRNA和蛋白水平。提示SINO和TG具有抑制关节炎症和关节破坏的作用,其作用机制可能是减少IL-6的产生,抑制B细胞的激活和分化。

The mechanism of immunosuppressive effect of sinominine on collagen induced arthritis of rat

To confirm the effect of sinominine(SINO) on joint destruction and to explore its possible mechanism of action,bovine collagen type II(CII) emulsified with Freund's incomplete adjuvant was injected intradermally at the base of tail of Wistar rats.When the swelling in the hind limb of rats occurred,they were randomly divided into 3 groups:saline control group;treatment group with SINO and treatment group with SINO + tripterygium glycoside(TG),and the swelling in the hind limbs was measured daily by cubic method.The whole body photography was taken by X ray mammography 35 days after application of drugs,Meanwhile,the erosion scoring system in 96 joints and the joint spacing narrow(JSN) scoring system in 100 joints were used to observe the joint destruction.The third proximal claw pad and lymph nodes in ingiunal groove were undergone pathlogical examination with HE staining,and the primary synoviocytes were cultivated in vitro.The content of IL-6 in the supernatants of cultures was determined by radioimmunological assay and the expression of IL-6 mRNA was detected by RT-PCR.It was demonstrated that SINO and TG could effciently suppress the development of joint swelling,bone erosion and changes in the joint interspace(P<0.01).In addition,they could also inhibit the hyperplasia of synoviocytes,cartilage destruction and reactions of germinal center and plasma cell infiltration in medullary cord of the collagen induced arthritis of rats(P<0.01).The expression levels of IL-6 protein and IL-6 mRNA in synoviocytes in this rat model were also reduced,but the effect of SINO was found to be inferior to that of TG.From these observation,it is apparent that SINO and TG could relieve the inflamatory responses and joint destruction in the collagen induced arthritis of rats through the reduced expression of IL-6,thus inhibiting the activation and differentiation of B lymphocytes.