中文摘要：

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。

英文摘要：

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.