氧化苦参碱对胶原蛋白诱导大鼠关节炎症及T细胞亚群的影响

Effects of Oxymatrine on Joint Inflammation and T Cell Subsets in Rats with Collagen Induced Arthritis

目的观察氧化苦参碱(oxymatrine,OMT)对Ⅱ型胶原蛋白诱导的关节炎(collagen induced arthritis,CIA)大鼠关节炎症及T细胞亚群的影响。方法将SD大鼠分为6组,正常对照组,模型对照组,雷公藤多苷片组以及OMT高、中、低剂量组,除正常对照组,其他5组建立大鼠胶原蛋白诱导的关节炎模型,自加强免疫后第1天分别灌胃给药4周,末次给药后取血,流式细胞仪检测T细胞亚群,ELISA法检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β;取关节滑膜4%多聚甲醛固定,观察滑膜病理改变情况。结果与模型组相比,OMT能降低关节炎指数评分(P<0.05),降低CD4+T细胞水平(P<0.05),升高CD8+T细胞水平(P<0.05),CD4+/CD8+比值降低(P<0.05),使促炎细胞因子TNF-α、IL-1β水平下调(P<0.01)。形态学观察OMT对滑膜细胞增殖有显著抑制作用。结论 OMT通过调节T细胞及细胞因子水平而发挥对类风湿性关节炎的治疗作用。

OBJECTIVE To study the effects of oxymatrine on joint inflammation and T cell subsets in CIA rats. METHODS Rats were randomly divided into 6 groups： normal control group, collagen-induced arthritis （CIA） model group, high-dose OMT （80 mg · kg-1· d-1 ）group, middle-dose OMT （40 mg · kg-1· d-1 ）group, low-dose OMT（20 mg · kg-1· d-1 ） group and total glucoside tripterygium （40 mgmg · kg-1· d-1）group. To establish CIA model, all rats were injected with mixture of sheep type Ⅱ collagen protein and Freund＇s complete adjuvant （FCA） intradennally at the right hindfoot, and injected again 1 week later at multipoints of the end of tail to boost the immunization. The intragastric administration procedure was performed from the first day after boosting immunization once a day for 4 weeks. Arthritis index （AI） was recorded every week. The blood sample was taken after the last administration to analyze T cell subsets by Flow Cytometry; serum TNF-α and IL-1β contents were measured by ELISA. Synovium of joint were fixed in 4% paraformaldehyde, and the hepatic pathological changes were observed. RESULTS OMT could improve arthritis index （P 〈 0. 05 ）, decrease CD4 ＋ T level （P 〈 0. 05 ） , increase CD8 ＋ T level （P 〈 0.05 ） , and also reduce CD4 ＋/CD8 ＋ ratio （P 〈 0. 05 ）. The levels of pro-ilfflammatory cytokines, TNF-α and IL-1β, were markedly decreased （P 〈 0. 01 ） , too. Morphological observation indicated that OMT had significant inhibitory effect on synovial ceils proliferation. CONCLUSION OMT may play a therapeutic action on rheumatoid arthritis through adjusting the levels of T cells and cytokine.