雷公藤甲素微乳凝胶外用治疗类风湿性关节炎的作用机理研究

项目名称： 雷公藤甲素微乳凝胶外用治疗类风湿性关节炎的作用机理研究

项目编号： No.81460607

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 管咏梅

作者单位： 江西中医药大学

项目金额： 48万元

中文摘要： 类风湿性关节炎(RA)是以关节滑膜炎为主要特征的常见自身免疫性疾病。 雷公藤是治疗 RA 疗效肯定的中药，雷公藤甲素是主要有效成分，其口服制剂疗效明确，但毒副作用严重限制了口服制剂的使用。雷公藤外用治疗 RA疗效好毒副作用少。20 世纪90年代以来开展了雷公藤外用的研究，仅涉及一般的药效学、透皮情况、促渗剂选用等，雷公藤外用治疗 RA的作用机理无文献报道。研究表明雷公藤外用对RA治疗作用不完全依赖血液中药物浓度。由于外用制剂是通过皮肤吸收，皮肤是一具有独特免疫功能的组织器官，皮肤树突状细胞/朗格汉氏细胞（LC）与免疫激活和免疫耐受关系密切,在调控机体免疫方面起着重要作用。本项目拟通过雷公藤甲素微乳凝胶外用，研究其在关节局部药动学，对滑膜细胞凋亡的影响，及对CIA大鼠皮肤LC数量形态、发生、分化、成熟等免疫功能的影响；以及对关节滑膜细胞免疫功能的影响，探讨经皮给药治疗RA作用机理。

中文关键词： 雷公藤甲素；微乳凝胶；类风湿性关节炎；作用机理

英文摘要： Rheumatoid arthritis (RA) is common autoimmune diseases mainly characterized by synovitis. Tripterygium Wilfordii has positive curative effect for RA, and the triptolide is the primary active ingredient, its oral preparations with unambiguous therapeutic effect, however, the toxic and side-effect of which severely limits the usage. Since 1990s, the study on the external application of Tripterygium Wilfordii has been developed, which only involved general pharmacodynamics, transdermal case, the option of penetration enhancer and so on. The mechanism of action in Tripterygium topical therapy for RA yet reported in the literature. Studies have shown that tripterygium topically used not entirely dependent on the drug concentration in blood for treatment of RA. As topical preparations were absorbed through the skin, which is a unique immune tissue organ, the dendritic cell/ Langerhans cells(LC) of skin has a close relationship with immune activation and immune tolerance, which plays the important role in the regulation of organ immune. The project proposed external application of triptolide microemulsion gel to study its pharmacokinetics in joints, the impact of synovial cell apoptosis, and effect on the number of CIA rat skin LC morphology, differentiation, maturation and other immune function, and the impact on the immune function of synovial cells, in order to investigate the mechanism of transdermal therapeutic effect of RA.

英文关键词： Triptolide;Microemulsion gel;Rheumatoid arthritis;Mechanism