自身免疫性心肌炎Th细胞亚群及其相关细胞因子的变化  

Immune State of Th1,Th2 and Th17 Subpopulation in Experimental Autoimmune Myocarditis

作　　者：韩丽娜[1] 李铁岭[2] 张亚晶[1] 杨庭树[1] 丁宇[1] 郭树理[1] 

机构地区：[1]中国人民解放军总医院南楼心血管一科,北京100853 [2]中国人民解放军总医院干部理疗科,北京100853

出　　处：《四川大学学报（医学版）》2011年第6期751-756,共6页Journal of Sichuan University(Medical Sciences)

基　　金：2007年北京市优秀人才培养资助个人项目(20071D1600200391);2008年北京市科技新星计划(B类)(2008B54)资助

摘　　要：目的了解辅助性T细胞Th1、Th2和Th17亚群在自身免疫性心肌炎的反应状态,从而探讨该病的免疫学发病机制。方法心肌C蛋白和完全弗氏佐剂足底注射、百日咳毒素腹腔内注射制作实验性自身免疫性心肌炎(EAM)大鼠模型。未给予免疫注射正常大鼠作为对照。在免疫注射后1周、2周、4周、6周和8周,经胸行心脏超声心动图检测。取心脏,行苏木素-伊红染色确定心肌炎症积分,天狼星红染色确定心肌纤维化。采用细胞内细胞因子染色和四色荧光抗体流式细胞术检测各组大鼠脾细胞中Th1、Th2和Th17比例,酶联免疫吸附试验检测外周血Th1相关细胞因子干扰素(IFN-)γ、Th2相关细胞因子白细胞介素(IL-)4和Th17相关细胞因子IL-17水平。结果经胸超声心动图显示EAM大鼠至免疫注射后第4周心脏射血分数维持正常值,左室收缩末期直径和左室舒张末期直径缩小;至第8周心脏射血分数明显降低,左室收缩末期直径和左室舒张末期直径增加。炎性积分在免疫注射后2周上调,4周达高峰,6周时逐渐降低;心肌纤维含量在第1周和第2周无明显改变,至第4周明显增强并达高峰,持续至第8周。脾细胞Th1及其相关细胞因子IFN-γ第1周反应血清水平升高,第4周达高峰,第6周开始下降。Th17及IL-17在第2～4周升高,水平维持至第6～8周。Th2在前4周无明显变化,IL-4在第4周开始升高,两者均在第6周迅速升高,并持续至第8周。结论在EAM大鼠模型中,2～4周是心肌炎症阶段,4～8周是纤维化阶段。在此过程中出现Th1/Th2失衡,其中炎症性心肌炎阶段以Th1、Th17亚群介导的细胞免疫为优势,纤维化心肌炎阶段以Th2和Th17亚群介导的体液免疫为优势,Th17衔接机体细胞免疫和体液免疫。Objective To shed light on changes in the gene expression of T helper lymphocyte（Th） subpopulation,Th1,Th2 and Th17 in autoimmune myocarditis and to gain insight into the immunological mechanisms underlying the essence of myocarditis.Methods An experimental Lewis rat autoimmune myocarditis model was induced by immunization with cardiac C protein and completed Freund adjuvant in double foot pads and subsequent intraperitoneal injection of pertussis toxin.Two groups of normal rats without immunological injection acted as control group.Transthoracic echocardiography was performed and subsequently hearts and spleens were obtained from EAM rats at 1 week,2 weeks,4 weeks,6 weeks and 8 weeks after immunization.The pathological sections of heart samples were prepared,the inflammatory score was determined by hematoxylin and eosin stain,the fibrosis score was determined by picrosirius red stain.The ratio of Th1,Th2 and Th17 subpopulation in spleen cells were measured by flow cytometry,and enzyme linked immunoabsorption assay（ELISA） was used to determine the serum level of Th1 related cytokine interferon-γ（IFN-γ）,Th2 related cytokine interleukin（IL）-4 and Th17 related cytokine IL-17.Results In EAM rats,cardiac ejection fraction remained normal until 4th week,and left ventricular end systolic diameter and left ventricular end diastolic diameter decreased.However,cardiac ejection fraction decreased obviously and left ventricular end systolic diameter and left ventricular end diastolic diameter rose until 8th week.Inflammatory score increased rapidly at 2nd week after immunization and remained peek level until 4th week and then gradually decreased at 6th and 8th week.Fibrosis score and fibrosis content increased from 4th week and maintained the peek level until 8th week.Ratio of Th1 in spleen cells of EAM rats and its related cytokine in serum,IFN-γ,increased at 1st week,arrived at the peek level until 4th week and gradually decreased at 6th week.Ratio of Th17 and IL-17 rose from 2nd-4th week and remained un

关 键 词：自身免疫性心肌炎 辅助性T细胞 辅助性T细胞相关细胞因子 

分 类 号：R542.21[医药卫生—心血管疾病]