SCN10A在心脏组织中的表达及其在心电生理中的作用  

Distribution of SCN10A in heart tissues and its role in cardiac electrophysiology

作　　者：段嘉霖 陶婧雯[1] 李林凌 刘念 阮燕菲 闻松男[2] 林立[1] 白融 王琳[1] DUAN Jialin;TAO Jingwen;LI Linling;LIU Nian;RUAN Yanfei;WEN Songnan;LIN Li;BAI Rong;WANG Lin(Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuban 430013, China)

机构地区：[1]华中科技大学同济医学院附属同济医院心血管内科,430013 [2]首都医科大学附属安贞医院-北京市心肺血管疾病研究所心内科

出　　处：《心肺血管病杂志》2018年第5期466-468,481,共4页Journal of Cardiovascular and Pulmonary Diseases

基　　金：北京市自然科学基金重点项目(7161003);国家自然科学基金面上项目(81770322);国家自然科学基金面上项目(81500254);国家自然科学基金面上项目(81670291);国家自然科学基金面上项目(81470465)

摘　　要：目的:从组织层面探究SCN10A在心肌组织中的分布及其在心脏电生理中的作用。方法:实验动物选择为标准Wistar大鼠和新西兰大耳兔。应用免疫组化的方法,探究SCN10A在心脏组织中的分布。使用兔楔形心肌块模型,将实验动物分为四组,分别为正常对照组、正常+A-803467组、ATX-II组和ATX-II+A-803467组,研究使用A-803467特异性阻断SCN10A,观察其对QT间期、动作电位时程(APD)、跨心室壁复极离散度(TDR)和心律失常事件发生率的影响。结果:免疫组化结果提示,在大鼠心脏组织中可见SCN10A表达。在兔楔形心肌块实验中,ATX-II+A-803467组较ATX-II组,其90%内膜动作电位时程(513.83 vs.760.09ms,P<0.05)和90%外膜动作电位时程(550.67 vs.809.19ms,P<0.05)均明显缩短,QT间期明显缩短(703.83 vs.1018.71ms,P<0.05),心律失常发生率也明显下降(0vs.57.1%,P<0.05)。结论:SCN10A在大鼠心脏组织中表达,特异性阻断SCN10A具有缩短动作电位时程、QT间期以及抗心律失常的作用。Objective： Our study is to investigate the distribution of SCN10A in cardiac tissues and its role in cardiac electrophysiology. Methods： A rabbit ventricular myocardial wedge model was used to detect the action potential duration,QT interval and ventricular arrhythmias before and after using A-803467,a highly selective blocker of SCN10A. The sodium channel opener ATX-II was used to induce a late sodium current because it is very small in normal condition. The expression of SCN10A in mouse and human cardiac tissues was identified by immunohistochemistry staining. Results： Our result showed that compared to ATX-II alone,A-803467/ATX-II shortened the action potential durations,QT intervals significantly. The ventricular arrhythmia events after programmed electrical stimulation were also reduced by treated with A-803467. Immunohistochemistry staining revealed that SCN10A was expressed not only within the myocardial cells where it was colocalized with α-actinin,but also in intracardiac neuronal which was costained by the neural markers Tubb3. Conclusion： Our result from this study demonstrated that Nav1. 8 channels,expressed in both myocardial cells and intracardiac neuronal,play an important role in myocardial electrophysiology.

关 键 词：离子通道 晚钠电流 室性心律失常 动作电位时程 QT间期 

分 类 号：R54[医药卫生—心血管疾病]