RANKL和M-CSF在CIA大鼠关节滑膜的表达及药物的干预作用  

Expression of RANKL and M-CSF in synovium of CIA rats and intervention of T-614 and methotrexate

作　　者：王茜茜[1] 王美美[2] 

机构地区：[1]东南大学医学院,南京210009 [2]东南大学附属中大医院风湿免疫科,南京210009

出　　处：《第三军医大学学报》2013年第17期1813-1817,共5页Journal of Third Military Medical University

基　　金：江苏省自然基金(BK2009276)~~

摘　　要：目的初步探讨RANKL和M-CSF在CIA大鼠关节滑膜的表达及T-614、MTX的干预作用。方法通过鸡Ⅱ型胶原和完全弗氏佐剂混合的胶原乳剂免疫大鼠,建立CIA大鼠模型,将CIA大鼠随机分为模型对照组、T-614组、MTX组和T-614+MTX组。药物干预组大鼠分别用T-614、MTX及T-614联合MTX干预3周。关节炎指数(arthritis index,AI)评分评价关节炎程度,HE染色观察踝关节组织形态学变化,X线片观察骨侵蚀情况,高频超声观察踝关节并测量滑膜厚度,Western blot法检测滑膜RANKL和M-CSF表达。结果与正常对照组相比,模型对照组AI评分、病理评分、X线评分、超声下滑膜厚度、关节滑膜RANKL,M-CSF表达均增加(P<0.05);与模型对照组相比,T-614组、MTX组、T-614联合MTX组上述观察指标均降低(P<0.05);与T-614组、MTX组相比,T-614联合MTX组上述观察指标均降低(P<0.05);T-614组和MTX组之间上述观察指标差异无统计学意义(P>0.05)。结论 RANKL和M-CSF参与了CIA大鼠关节滑膜病变的发生、发展,T-614、MTX可能通过减少细胞因子RANKL,M-CSF的生成来延缓关节滑膜病变的进展,T-614与MTX具有一定的协同效应。Objective To investigate the expression of RANKL and M-CSF in the synovium of collagen-induced arthritis （CIA） rats and the intervention of T-614 and methotrexate （MTX） on their expression. Methods The CIA animal models （n=40） were established by injecting type Ⅱ collagen and complete Freud’s adjuvant, and then were divided randomly into 4 groups, including a model group （n=10）, a MTX group （n=10）, a T-614 group and a MTX＋T-614 group （n=10）. Arthritis was evaluated by arthritis index （AI）. The expression of RANKL and M-CSF in the synovium was detected by Western blotting. The synovial pathological score of ankle joints, the radiographic changes and synovial thickness were evaluated. Results The arthritis index, the expression of RANKL and M-CSF in the synovium, the synovial pathological score, the X-ray score and the synovial thickness were increased in the model control group, the MTX group, the T-614 group and the MTX＋T-614 group as compared to the normal control group （P〈0.05）. Compared with the model control group, all above indices were significantly decreased in the MTX group, the T-614 group and the MTX＋T-614 group （P〈0.05）. Compared with the MTX group and the T-614 group, all above indices were decreased in the MTX＋T-614 group （P〈0.05）. No difference was found in these indices between the MTX and T-614 groups （P〉0.05）. Conclusion RANKL and M-CSF are involved in the occurrence and development of joint synovitis in CIA rats. T-614 and MTX can delay the inflammation and bone/cartilage destruction in joint synovitis by synergistically suppressing the expression of RANKL and M-CSF.

关 键 词：胶原诱导性关节炎 大鼠 艾拉莫德 甲氨蝶呤 

分 类 号：R392.3[医药卫生—免疫学] R593.22[医药卫生—基础医学]