共刺激分子CTLA-4与B7在自身免疫性心肌炎中的作用

摘要

目的:研究共刺激分子CTLA-4、B7-1和B7-2在实验性自身免疫性心肌炎(EAM)组织中的表达及变化,探讨EAM的发病机制.方法:注射猪心肌球蛋白免疫Lewis大鼠建立EAM模型(实验组,n=30),按不同时间段随机分成14、28、56天3个亚组,取各组心脏组织行HE染色观察心肌的病理变化,免疫组化与实时荧光定量PCR技术检测心脏组织CTLA-4、CD80、CD86及其mRNA的表达.结果:实验组大鼠均出现不同程度的心肌炎改变；免疫组化染色示CD80、CD86蛋白主要见于实验组心脏组织的炎性细胞中.于初次免疫的第14至28天表达增强,56天时表达减弱.Real Time-PCR检测结果表明实验组心脏组织CD80、CD86的mRNA表达水平比正常对照组明显增加(P＜0.05).结论:共刺激分子CTLA4、CD80、CD86的表达增加促进了心脏组织的炎症反应,与EAM的发生发展密切相关.%Objective: Study the expression and changes of costimulatory molecule CTLA-4, B7-1 and B7-2 in experimental autoimmune myocarditis ( EAM) and explore the pathogenesis of EAM. Methods: EAM model was established by injecting porcine cardiac myosin into Lewis rats(experimental group, n =30) ,and then the 30 rats were randomly divided into three subgroups in accordance with 14 d, 28 d, 56 d after the first immunization . HE staining was used to observe the change of histopathological characteristics. Im-munohistochemical staining and real-time fluorescence quantitative PCR detection was used to analysis the expression of CTLA-4, CD80, CD86. Results:There were varying degrees of myocarditis change in experimental group; CTLA-4, CD80, CD86 mainly expressed in cardiac cells. After the first immunization, expression of proteins increased gradually from 14 d to 28 d, but decreased in 56 d. Real-time PCR: compared with normal group, the expression of CD80, CD86 mRNA were higher in experimental group ( P < 0. 05 ) . Conclusion: The expression of CD80, CD86 and CTLA-4 promotes heart tissue inflammation, and may closely related to the occurrence and development of EAM.