抗心律失常肽在兔肥厚心肌心律失常中的作用

目的:研究缝隙连接开放剂抗心律失常肽(AAP10)抗肥厚心肌室性心律失常的作用并探讨缝隙连接蛋白43(Cx43)与心律失常的关系.方法:30只日本大耳白兔随机分为假手术组(Sham组)、左室肥厚组(LVH组)、AAP10组.LVH组和AAP10组行腹主动脉缩窄术,Sham组开腹但不行腹主动脉缩窄术.术后喂养8周.制备左室楔形心肌块灌注模型.Sham组和LVH组灌注正常台式液,AAP10组灌注含100 nmol/L的AAP10台式液.利用浮置玻璃微电极法同步记录楔型心肌块跨壁心电图和内外膜心肌细胞跨膜动作电位,程序电刺激起搏,记录早期后除极及室性心律失常的发生率.采取Western blot检测3组Cx43表达;采取免疫荧光方法显示3组Cx43的分布.结果:Sham组、LVH组、AAP10组室性心律失常的发生率分别为0、40%、10%.与Sham组相比,LVH组Cx43表达下降(50.7±6.1)%(P＜0.05),AAP10组与LVH组相比,Cx43表达上升(20.9±4.7)%,P＜0.05.免疫荧光显示肥厚心肌Cx43分布紊乱,由正常的端端分布成为细胞表面随机分布,加入AAP10后可改善其分布.结论:肥厚心肌有较高的心律失常发生率,肥厚心肌细胞Cx43表达下降并且排列紊乱,AAP10可提高Cx43的表达及改善其分布,降低室性心律失常的发生率.

Effect of antiarrhythmic peptide on ventricular arrhythmias in rabbits with hypertrophic myocardium

Objective:To investigate the effect of antiarrhythmic peptide(AAP10) on ventricular arrhythmia in rabbits with hypertrophic myocardium,and the relationship between gap junction(mainly consistent by connexin43) and ventricular arrhythmia.Methods:All rabbits were randomly divided into sham-operation(Sham),cardiac hypertrophy(CH),and AAP10 group.In CH and AAP10 groups,abdominal aorta were partially constricted to make hypertrophic heart of rabbit modes,while in Sham group,the abdominal aortas were only exposed without constriction.All rabbits were fed twelve weeks.By using arterially perfused rabbit ventricular wedge preparation,transmembrance action potentials were recorded simultaneously from endocardium to pericardium together with a transmural ECG by using of two separate intracellular floating microelectrodes.The incidence of early after depolarization(EAD) and ventricular arrhythmia(VA) were recorded.Expression of Cx43 was evaluated by western-blot.The distribution of Cx43 was observed by confocal immunofluorescence microscopy.Result:Incidences of VA in those groups were 0,40%,10% respectively.The Cx43 was decreased in LVH group(P<0.05) and the distribution of Cx43 is disorder around the myocytes.AAP10 can increase the expression of Cx43 in AAP10 group,also can rebuild the distribution of Cx43 in it.Conclusion:AAP10 can improve intercellular communication by increase the expression of Cx43 and rebuild the distribution of Cx43,which result in lower the incidence of EAD and ventricular arrhythmia.