抗胶原Ⅱ功能域抗体诱导的RA样小鼠模型的建立及其免疫病理学指标分析  

The molecular mechanism of IFN-βintervention in the RA-like mice model induced by anti-collagenⅡfunctional domains antibody

作　　者：赵蓉[1] 许荣 周晓薇[1] 苗平[1] 钱柳[1] 余奇文[1] 张继英[1] 陈雪华[3] 张冬青[1] 

机构地区：[1]上海交通大学医学院,上海市免疫学研究所,上海200025 [2]上海市长宁区光华中西医结合医院,上海200052 [3]上海交通大学医学院附属瑞金医院,上海200025

出　　处：《现代免疫学》2013年第1期6-11,共6页Current Immunology

基　　金：国家自然基金(31270963);上海市科委重点资助项目(10JC1408500;10ZR1426100)

摘　　要：应用IFN-β药物干预由抗胶原Ⅱ功能域抗体诱导建立的类风湿性关节炎(rheumatoid arthritis,RA)样小模型(CAIA),揭示RA发病可能的新靶点以及为将IFN-β药物用于RA患者以调节其免疫功能紊乱和骨代谢失衡提供新的理论和实验依据。本研究采用不同浓度的抗胶原Ⅱ功能域抗体诱导BAIB/c小鼠,建立RA样动物模型,通过观察其外观、关节评分以及番红固绿和HE染色并与正常对照组比较来评估该模型的成功建立:采用RT-PCR和免疫组化等技术检测各组模型小鼠与免疫功能紊乱和骨质破坏密切相关的MMP-3、MMP-3/TIMP-1、RANKL及c-Fos分子的表达水平。研究发现CAIA组模型小鼠上述各炎症分子的表达均显著高于对照组小鼠,同时利用重组鼠源性IFN-β调控该模型,发现其能缓解CAIA小鼠的发病情况,证明IFN-β具有使RA样小鼠免疫功能重建以及阻抑模型小鼠骨破坏的生物学作用,为进一步深入研究其调控机制和尽快将IFN-β用于临床RA的治疗奠定了实验基础。In order to find a novel therapeutic target of rheumatoid arthritis(RA) and provide a new theoretical and experimental basis for clinical intervention of IFN-βin RA patients,we first established a RA-like mouse model(CAIA) by injection of the antibody against the functional domains of collagenⅡinto BALB/c mice.The validity of the model was evaluated by observing external appearance,arthritis score,safranin O staining,and hematoxylin and eosin staining of the joint tissues.RTPCR and immunohistochemistry were used to detect the expression levels of MMP-3,MMP-3/TIMP-1,RANKL and c-Fos which were known all closely related to immune dysfunction and bone damage in RA patients.We found that the levels of in- flammatory molecules in the CAIA group were significantly higher than those in the normal group and recombinant murine IFN-βcould alleviate the morbidity of CAIA mice.These results proved that IFN-βplayed biological roles in the immune reconstitution and inhibition of bone destruction in RA-like mice,which lay a foundation for further studying the regulatory mechanism of IFN-βand its potential application in clinical treatment of RA.

关 键 词：CAIA IFN—β c—Fos 骨平衡 

分 类 号：R392.9[医药卫生—免疫学]