酒精性心肌病小鼠心电图校正QT间期延长的电生理机制探讨  

The Electrophysiological Mechanism of QT Prolongation in Experimental Mice With Alcoholic Cardiomyopathy

作　　者：江宇[1] 韩钟霖 曹克将[1] 汪道武[1] 

机构地区：[1]南京医科大学第一附属医院心血管内科,江苏省南京市210029

出　　处：《中国循环杂志》2015年第4期374-378,共5页Chinese Circulation Journal

基　　金：国家自然科学基金面上项目(81170159);江苏省六大人才高峰资助项目(2012-WS-018)

摘　　要：目的:通过建立酒精性心肌病小鼠动物模型,研究酒精性心肌病小鼠校正QT间期(QTc)延长的电生理机制。方法:将40只C57 BL/6小鼠随机分为两组,酒精组(n=25)和对照组(n=15)。酒精组通过长期饮酒和灌胃建立小鼠酒精性心肌病模型,因造模和麻醉过程中死亡12只小鼠,最终纳入13只小鼠,对照组麻醉过程中死亡3只小鼠,最终纳入12只。使用染色和电镜验证酒精性心肌病模型,用小动物心电图测量小鼠心电图相关指标,通过酶解法将小鼠心室肌细胞进行急性分离,最后使用全细胞膜片钳技术对细胞动作电位以及各种离子通道进行电生理学检测,并进行通道相关动力学急性检测。结果:5个月后,酒精组小鼠平均左心室射血分数(LVEF)值为(39.06±1.511)%,而对照组小鼠为(61.18±2.56)%。小鼠心电图检查显示,酒精组平均QTc较对照组明显延长[(106.43±5.91)ms vs(85.64±6.35)ms,P<0.05]。全细胞膜片钳实验发现,酒精组小鼠心肌细胞动作电位时程延长,心肌细胞动作电位复极至90%所需时间(APD_(90))为(37.62±3.53)ms,对照组小鼠心肌细胞APD_(90)为(25.77±3.41)ms。膜片钳实验发现酒精组小鼠L型钙电流失活延迟,其窗口电流面积增大。结论:长期大量饮酒可导致心室肌钙通道失活延迟,从而延长心室肌细胞动作电位。这是酒精性心肌病小鼠心电图QTc延长的原因之一。Objective： To investigate the electrophysiological mechanism of QT prolongation in experimental mice with alcoholic cardiomyopathy （ACM）. Methods： A total of 40 C57BL/6 mice were randomly divided into 2 groups：Alcoholic group, n=25, the ACM model was established by long term alcohol drinking and intragastric alcohol administration, 12 mice died during modeling and anesthesia and 13 mice were enrolled for study. Control group, n=15, the mice were fed by normal diet, 3 died during anesthesia and 12 were enrolled for study. All animals were treated for 5 months. The pathological changes of ACM were examined by electric microscope, QT interval was measured by ECG, the electrophysiology of cell action potential duration and ion channels were detected by whole cell patch-clamp techniques. Results： Alcohol group showed decreased left ventricle ejection fraction （LVEF） than Control group （39.06 ± 1.511）%vs （61.18 ± 2.56）%, prolonged QT interval （106.43 ± 5.91） ms vs （85.64 ± 6.35） ms, P〈0.05, and extended action potential duration APD90 （37.62 ± 3.53） ms vs （25.77 ± 3.41） ms. Alcohol group also presented delayed voltage-dependent inactivation of L-type Ca^2＋channel and increased window current area. Conclusion： Long term alcohol drinking may cause extended inactivation of myocardium Ca^2＋channel, prolong the action potential duration, which is one of the mechanisms for prolonged QT interval of ACM in experimental mice.

关 键 词：酒精性心肌病 校正QT间期 膜片钳实验 动作电位 L型钙电流 

分 类 号：R54[医药卫生—心血管疾病]