血管紧张素Ⅱ1型受体自身抗体与心钠肽在甲亢心肌肥大大鼠中的表达  

Analysis on angiotensin Ⅱ type 1 receptor agonistic autoantibody and expression of ANP in hyperthyroidism with cardiac hypertrophy

作　　者：徐金玲[1] 赵林双[2] 王敏[3] 

机构地区：[1]南方医科大学武汉临床医学院,武汉430070 [2]广州军区武汉总医院内分泌科,武汉430070 [3]华中科技大学同济医学院附属协和医院心血管病研究所,武汉430020

出　　处：《中国免疫学杂志》2014年第2期173-177,181,共6页Chinese Journal of Immunology

基　　金：武汉市科技局应用基础研究计划项目(2013060602010244)

摘　　要：目的：探讨甲亢心肌肥大大鼠中血清抗血管紧张素Ⅱ1型受体自身抗体（AT1-AA）的产生及变化特征及其与心肌肥大特征性基因心钠肽（ANP）表达的关系.方法：制备甲亢大鼠模型,分别于实验2、4和8周留取血标本及心肌组织标本,应用酶联免疫吸附试验（ELISA）方法检测大鼠血清中AT1-AA,动态观察心脏指数（HWI）、心肌细胞直径（MD）、心肌胶原容积分数（CVF）及心肌组织病理改变,采用RT-PCR法检测心肌组织ANP mRNA和放射免疫法检测血浆ANP水平的表达情况.结果：（1）甲亢组大鼠在实验2周时HMI即明显增加,并随时间延长进一步加重,光镜下可见心肌细胞肥大,发生严重胶原纤维化,MD和CVF显著增加,表明甲亢大鼠心肌肥大模型建立成功;（2）甲亢组大鼠血清中AT1-AA吸光度值在实验2周即有明显升高,之后逐渐上升至实验结束时,与同期对照组相比差异均有统计学意义（P＜0.05）,提示AT1-AA表现出随甲亢心肌肥大病变加重而逐渐升高的变化规律;（3）甲亢组大鼠心肌组织ANP mRNA表达较同期对照组明显升高（均P＜0.05）,且随着病程的延长,呈进行性升高,血浆中ANP水平变化趋势与其一致,说明AT1-AA可能会引起ANP表达增加;（4）线性相关分析显示,甲亢组大鼠血清AT1-AA与心肌肥大相关指标HWI、DM、CVF、血浆ANP和心肌组织ANP mRNA呈显著正相关（r =0.649 ～0.749;均P＜0.05）.结论：甲亢心肌肥大大鼠AT1-AA可引起ANP表达增加,AT1-AA介导的免疫反应参与甲亢心肌肥大的病理生理过程.Objective：To observe the production and variation characteristics of agonistic autoantibody against angiotensin Ⅱ type 1 receptor （AT1-AA） during progression of hyperthyroidism with cardiac hypertrophy,and the relationship between AT1-AA and atrial natriuretic peptide （ANP）.Methods：Blood and heart samples were collected from hyperthyroidism rats models at 2,4 and 8 weeks.AT1-AA in the sera of rats were detected by ELISA ; HWI （HW/BW）,myocyte diameter （MD）,collagen volume fraction （CVF） and pathological changes in myocardium were dynamically observed.The level of ANP were determined by radioimmunoassay and RT-PCR.Results：（1） In hyperthyroidism group,HWI was remarkably increased at 2 weeks and aggravated with time ; cardiac hypertrophy and severe collagen fibrosis were observed at the light microscopic level; DM and CVF were also increased significantly.（2） Compared with the control group at the same period,the OD value of AT1-AA in the sera of hyperthyroidism rats was remarkably increased after 2 weeks and gradually increased until the ending of the present experiment（all P ＜ 0.05）.（3） Compared with the control group,the expression of ANP mRNA in hyperthyroidism group was enhanced significantly and risen progressively with the duration of the experiment,which was consistent with the trend of plasma ANP levels.（4） Linear correlation analysis showed that the serum AT1-AA level was correlated positively with HWI,DM,CVF,plasma ANP and myocardium ANP mRNA in hyperthyroidism rats（r =0.649-0.749,all P ＜ 0.05）.Conclusion：The serum AT1-AA in rats of hyperthyroidism with cardiac hypertrophy may cause the increased expression of ANP,AT1-AA plays an important role in hyperthyroidism with cardiac hypertrophy.

关 键 词：血管紧张素Ⅱ1型受体 自身抗体 甲亢 心肌肥大 心钠肽 

分 类 号：R392.7[医药卫生—免疫学] R581.1[医药卫生—基础医学]