蛋白激酶C激动剂致心律失常作用机制的研究  

Mechanism of cardiac arrhythmogenesis induced by protein kinase C activation

作　　者：倪明科 张存泰[1] 李连东[1] 阮磊[1] 王琳[3] 

机构地区：[1]华中科技大学同济医学院附属同济医院综合科,武汉430030 [2]湖北省中山医院心内科,武汉430030 [3]华中科技大学同济医学院附属同济医院心内科

出　　处：《临床心血管病杂志》2010年第8期570-573,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助课题(No:30770879)

摘　　要：目的:观察蛋白激酶C激动剂佛波酯(PMA)对兔室性心律失常的影响并探讨其作用机制。方法:制备左室楔形心肌块灌注模型,随机分为正常对照组(灌流台氏液),PMA组(灌流台氏液+PMA500nmol/L)。采用浮置玻璃微电极法同步记录心内膜、心外膜心肌细胞跨膜动作电位及跨室壁心电图,给予程序性期前刺激诱发室性心动过速的发生。通过免疫印迹法(Western blot)检测心肌细胞缝隙连接蛋白43(Cx43)总量及其S368位点去磷酸化(NP-Cx43S368)蛋白水平的变化。结果:与正常对照组相比,PMA组QT间期显著缩短[(260±25)ms:(302±21)ms,P<0.01],T波顶点至终点的间期、T波顶点至终点的间期与QT间期的比值显著增大[(61±13)ms:(51±7)ms、0.24±0.05:0.17±0.02,均P<0.01],Cx43的总量、NP-Cx43S368蛋白水平显著减少(分别为P<0.05、P<0.01);与正常对照组相比,PMA组明显增加了室性心动过速诱发率(70.0%:0%,P<0.05)。结论:PMA通过下调心肌缝隙连接的总量及功能从而导致心律失常的发生。Objective：To observe the effect of protein kinase C agonist,phorbol ester （PMA） on rabbit ventricular arrhythmia and to investigate its mechanism.Method：An arterially-perfused rabbit left ventricular preparation were was randomly assigned to control and PMA 500 nmol/L groups.Transmural ECG as well as action potential from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments.Changes of Cx43 and dephosphorylated Cx43 on S368 was were measured by Western blot.Result：Compared with the control group,the QT interval （260±25 ms vs 302±21 ms,P0.01） was shortened significantly in the PMA group as well as a significant increase of Tp-e [（61±13） ms vs （51±7） ms,P0.01] and Tp-e/QT （0.24±0.05 vs 0.17±0.02,P0.01）;PMA led a significant decrese of connexin43 （P0.05） and nonphosphorylated connexin43 at S368 （P0.01）;Nonsustained ventricular tachycardia （VT） could be induced in six out of ten animals in the PMA group （70.0% vs 0%,P0.01）.Conclusion：Down-regulation of cardiac gap junction by protein kinase C activation contributes to arrhythmogenesis in rabbit left ventricular wedge.

关 键 词：心律失常 佛波酯 QT间期 跨室壁复极离散度 左室楔型心肌组织块 缝隙连接 

分 类 号：R541.7[医药卫生—心血管疾病]