甲氨蝶呤对小鼠胶原诱导性关节炎的治疗作用及其机制  

Methotrexate inhibited the development of collagen-induced arthritis in mice by decreasing the ratio of Th17/Treg cells

作　　者：孙梦怡[1] 吴卫疆[1,2] 许惠玲[1] 刘霞[1] 夏圣[1] 邵启祥[1] 

机构地区：[1]江苏大学基础医学与医学技术学院免疫学与免疫检验学系,江苏镇江212013 [2]江苏大学基础医学与医学技术学院组织胚胎学系,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2012年第4期291-294,共4页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(30671984);江苏省自然科学基金资助项目(BK2008231;CXZZ11-0591)

摘　　要：目的:研究甲氨蝶呤关节周围注射后对小鼠胶原诱导性关节炎(collagen-induced arthritis,CIA)的治疗作用及其机制。方法:从初次免疫后第22天开始至50天止,每周3次关节周围注射甲氨蝶呤,PBS作阴性对照,对CIA小鼠关节炎严重程度进行评分并比较各组关节炎发生率,石蜡切片观察组织病理学变化,流式细胞术检测腹股沟淋巴结细胞中Th17细胞与Treg细胞的比例变化情况。结果:甲氨蝶呤可以有效降低小鼠关节炎的发病率及平均关节炎指数(P<0.001);石蜡切片显示甲氨蝶呤对炎症细胞浸润、血管翳的形成、软骨以及骨的破坏具有较好的抑制作用;流式细胞术检测显示甲氨蝶呤组Th17细胞比例降低,Treg细胞比例增加(P<0.05)。结论:甲氨蝶呤关节周围注射可以有效抑制类风湿关节炎的发展,其机制可能与下调Th17/Treg细胞的比率有关。Objective： To investigate the therapeutic effect of methotrexate（MTX） to mouse collagen-induced arthritis（CIA） and its possible mechanism.Methods： MTX was injected into local joint of CIA mice three times a week from the 22nd day to the 50th day after primary immunization,and PBS was set up as negative control.The incidence and arthritis score in joint were calculated and compared between each group.The histopathological changes were evaluated in paraffin sections.The percent of Th17 cells and Treg cells in inguinal lymph nodes were analyzed by Flow cytometry（FCM）.Results： MTX reduced the arthritis incidence and severity score of CIA mice effectively（P〈0.001）.Paraffin sections showed that MTX inhibited the inflammatory cells infiltration,pannus formation,and destruction of cartilage and bone.MTX decreased the percent of Th17 cells and increased the percent of Treg cells effectively（P〈0.05）.Conclusion： MTX inhibited the development of rheumatoid arthritis effectively.The mechanism may be involved in which the ratio of Th17/Treg cells was decreased.

关 键 词：甲氨蝶呤 类风湿关节炎 胶原诱导性关节炎 TH17细胞 TREG细胞 

分 类 号：R979.5[医药卫生—药品]