RANKL/OPG系统与大鼠Ⅱ型胶原诱导性关节炎发病的关系及^(99)锝-亚甲基二膦酸盐的干预作用  

Relationship between RANKL/OPG system and type Ⅱ collagen-induced arthritis in rats and the intervention of [^(99)Tc]-methylene diphosphonate

作　　者：景丽娟[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：《中国药科大学学报》2011年第3期251-254,共4页Journal of China Pharmaceutical University

摘　　要：探讨核因子κB受体活化因子配体/骨保护素(RANKL/OPG)系统与大鼠Ⅱ型胶原诱导性关节炎(CIA)发病的关系及99锝-亚甲基二膦酸盐(99Tc-MDP,商品名:云克)的干预作用。除正常对照组(n=8)外,其余大鼠建立CIA模型,随机分为模型组、甲氨蝶呤(MTX)组和云克组。采用关节炎指数(AI)评分评价关节炎程度;ELISA法检测关节液RANKL、OPG水平;观察膝关节病理变化;免疫组化法检测膝关节滑膜RANKL、OPG表达。结果表明,与正常对照组相比,模型组及干预组AI评分、关节液RANKL和OPG浓度、膝关节滑膜RANKL和OPG表达均显著增加(P<0.01),干预组上述指标均明显低于模型组(P<0.01),云克组明显低于MTX组(P<0.01)。结果表明,RANKL/OPG系统参与了大鼠C IA关节破坏的发生发展;云克可能通过抑制CIA大鼠的RANKL、OPG表达、降低RANKL/OPG比值起延缓关节破坏的作用,其起效时间明显早于甲氨蝶呤。The relationship between RANKL/OPG（receptor activator of nuclear factor-κB ligand/ osteoprotegerin） system and type Ⅱcollagen-induced arthritis in rats and the effects of [ ^99Tc ]-methylene diphosphonate（99Tc-MDP） were explored.The collagen-induced arthritis（CIA） model was established by subcutaneous injection with type Ⅱ collagen and complete Freud＇s adjuvant to rats,except the normal group（n=8）.The rats that successfully developed CIA（n=24） were divided into three groups randomly：model group（n=8）,99Tc-MDP-treated group（n=8） and methotrexate（MTX）-treated group（n=8）.The severity of arthritis was quantitated by measurement of arthritis index;the levels of RANKL/OPG in synovial fluid were tested by ELISA;and the expression of RANKL/OPG on synovial membrane was tested by immunohistochemistry.The arthritis index,the concentrations of RANKL and OPG in synovial fluid and their expression on synovial membrane increased in model group,99Tc-MDP-treated group and MTX-treated group compared with normal group（P〈0.01）.99Tc-MDP and MTX treatment prevented the increase of all indexes above（P〈0.01）,furthermore,the indexes in 99Tc-MDP-treated group were notably lower than those of the MTX-treated group（P〈0.01）.It was concluded that RANKL and OPG played a role in lesions of synovial membrane,cartilage and bone of CIA rats,and that 99Tc-MDP might relieve the injury of synovial membrane,cartilage and bone through inhibiting the expression of RANKL and OPG and decreasing the ratio of RANKL/OPG,and 99Tc-MDP was better than MTX in relieving synovial lesions,cartilage damage and bone erosion.

关 键 词：类风湿关节炎 胶原诱导性关节炎 ^99锝-亚甲基二膦酸盐 甲氨蝶呤 核因子ΚB受体活化因子配体 骨保护素 

分 类 号：R593.22[医药卫生—内科学]