大青鲨Ⅱ型胶原蛋白灌胃诱导免疫耐受治疗类风湿关节炎  

Treatment of rheumatoid arthritis with immune tolerance induced by gavage shark type Ⅱ collagen in rats

作　　者：陈丽娟[1,2] 包斌[1] 卜永士[1] 王南平[3] 谢晶[1] 吴文惠[1,4] 

机构地区：[1]上海海洋大学食品学院海洋药物教研室上海水产品加工及贮藏工程技术研究中心,上海201306 [2]上海市水产研究所水产品加工研究室,上海201306 [3]中国科学院深圳先进技术研究院人体组织与器官退行性研究中心,深圳518055 [4]上海海洋大学海洋科学研究院海洋药物与健康食品研究所,上海201306

出　　处：《药学服务与研究》2013年第4期265-269,共5页Pharmaceutical Care and Research

基　　金：国家高技术研究发展计划(2011AA09070109);上海市科学技术委员会计划项目(11DZ2280300)

摘　　要：目的:研究大青鲨Ⅱ型胶原蛋白(shark typeⅡcollagen,SCⅡ)灌胃诱导免疫耐受治疗类风湿关节炎(rheumatoidarthritis,RA)的疗效和机制。方法:60只大鼠随机分为6组,除空白对照组以外的其他大鼠以弗式完全佐剂诱导RA模型。模型对照组大鼠灌服0.2ml浓度为0.05mol/L的乙酸溶液,其余各组大鼠分别灌服0.2ml 1mg/ml牛源Ⅱ型胶原蛋白(bovine typeⅡcollagen,BCⅡ)、1和3mg/ml SCⅡ、10mg/ml雷公藤多苷溶液(均以0.05mol/L乙酸溶液为溶剂)诱导免疫耐受。以迟发型超敏反应、循环免疫复合物、白介素-10血清水平、踝关节组织形态学和软骨表面修复状况共5个指标来评价SCⅡ治疗RA的疗效。通过体外细胞实验研究SCⅡ诱导免疫耐受的机制。结果:SCⅡ能通过灌胃诱导免疫耐受,减少迟发型超敏反应,使循环免疫复合物呈阴性,显著提高白介素-10的水平,修复踝关节软骨表面损伤,显著增加CD4+T淋巴细胞Fas/Apo-1的数量。SCⅡ治疗RA的疗效优于雷公藤多苷和BCⅡ,最佳剂量为3mg.kg-1.d-1。结论:RA大鼠模型灌胃SCⅡ可诱导免疫耐受,对RA有较好疗效。Objective：To investigate the efficacy of immune tolerance induced by garage shark type 11 collagen （SCI） on rheumatoid arthritis （RA） in rats and its mechanism. Methods： Sixty rats were randomly divided into 6 groups. Except those rats in the blank control group, all the remaining rats were induced by Freund complete adjuvant to develop RA models. Rats in the model control group were gavaged with 0.2 ml of 0.05 mol/L acetic acid solution, while rats in the other groups were ga- raged with 0. 2 ml of 1 mg/ml bovine type Ⅲ collgen （BC ]][ ）, 1 mg/ml SC Ⅱ , 3 mg/ml SC H , 10 mg/ml tripterygium polygly cosides respectively to induce immune tolerance. The efficacy of SC Ⅱ on RA was evaluated by the following 5 parameters： de- layed hypersensitivity, the level of circulating immune complexes, the serum level of interleukin 10, histomorphology of ankle joint and the repair of ankle cartilage tissue. The mechanism of immune tolerance induced by SC Ⅱ was studied by in vitro cell experiment. Results： Gavage administration of SC Ⅱ could induce immune tolerance, decrease delayed hypersensitivity, make circulating immune complexes negative, increase the serum level of interleukin-10, repair the damaged ankle cartilage tissue and increase the amount of Fas/Apo 1 in T cells. The efficacy of SCⅡ with an optimal dose of 3 mg·kg-1·d-1 was superior to BC Ⅱ and tripterygium polyglycosides in the treatment of RA. Conclusion： In the RA rat model, gavage of SC Ⅱ could induce immune tolerance, which could produce effect on RA.

关 键 词：关节炎 类风湿 胶原蛋白 Ⅱ型 大青鲨 免疫耐受 

分 类 号：R593.22[医药卫生—内科学]