抗心律失常肽对蛋白激酶C激动剂致心律失常作用的影响  

Effects of Antiarrhythmic Peptide on Cardiac Arrhythmogenesis Induced by Protein Kinase C Activation

作　　者：倪明科[1,2] 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,武汉430030

出　　处：《华中科技大学学报（医学版）》2010年第5期595-599,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30770879)

摘　　要：目的观察抗心律失常肽对蛋白激酶C激动剂致心律失常作用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①正常组;②佛波酯(PMA)组:PMA 0.5μmol/L;③抗心律失常肽(AAP10)组:PMA0.5μmol/L+AAP10 0.5μmol/L。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(室速)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位点去磷酸化水平的变化。结果与正常对照组相比,PMA组QT间期[(260±25)ms vs.(302±21)ms,P<0.01]显著缩短,Tp-e(同一心搏T波顶点至终点的间期)[(61±13)ms vs.(51±7)ms,P<0.01]及Tp-e/QT[(0.24±0.05)vs.(0.17±0.02),P<0.01]显著增大,Cx43的总量(P<0.05)及S368位点去磷酸化水平(P<0.01)显著减少,室速诱发率(70%vs.0%,P<0.05)明显增加。与PMA组相比,AAP10组QT间期[(241±22)ms vs.(260±25)ms,P>0.05]及S368位点去磷酸化水平(P>0.05)无明显改变,但Cx43的总量(P<0.05)明显增加,Tp-e[(41±6)ms vs.(61±13)ms,P<0.01]及Tp-e/QT[(0.17±0.03)vs.(0.24±0.05),P<0.01]显著减小,且室速诱发率(20%vs.70%,P<0.05)明显降低。结论 AAP10通过阻止PMA对缝隙连接的下调而减少PMA诱导的兔室性心律失常的发生。Objective To observe the effects of antiarrhythmic peptide on cardiac arrhythmogenesis induced by protein kinase C activation and to investigate its mechanism.Methods The arterially-perfused rabbit left ventricular models in rabbits were established and randomly divided into control group,PMA（0.5 μmol/L）group,and PMA（0.5 μmol/L）＋AAP10（0.5 μmol/L）group.Transmural ECG as well as action potential from both endocardium and epicardium was simultaneously recorded.Programmed electrical stimulation（PES）was applied to induce ventricular tachycardia（VT）.Changes of Cx43 and nonphosphorylated Cx43 on S368 was measured by Western blot.Results As compared with control group,the QT interval[（260±25）ms vs.（302±21） ms,P〈0.01]was shortened significantly,Tp-e（the time from the peak of the T wave to the point at which the final downs-lope of the T wave crossed the isoelectric line）[（61±13）ms vs.（51±7） ms,P〈0.01]and Tp-e/QT[（0.24±0.05） vs.（0.17±0.02）,P〈0.01]increased,the amount of connexin43（P〈0.05）and nonphosphorylated connexin43 on S368（P〈0.01）decreased,the incidence of VT increased（70% vs.0%,P〈0.05）in PMA group.There was no significant difference in the QT interval[（241±22）ms vs.（260±25） ms,P〉0.05]and the amount of nonphosphorylated connexin43 on S368（P〈0.05）between PMA group and AAP10 group.However,the Tp-e[（41±6）ms vs.（61±13） ms,P〈0.01]and Tp-e/QT[（0.17±0.03） vs.（0.24±0.05）,P〈0.01]were increased,the amount of connexin43（P〈0.05）decreased and the incidence of VT decreased（20% vs.70%,P〈0.05）in AAP10 group as compared with PMA group.Conclusion AAP10 can prevent PMA-induced rabbit ventricular arrhythmias by attenuating the down-regulation of cardiac gap junction.

关 键 词：抗心律失常肽 佛波酯 QT间期 跨室壁复极离散度 缝隙连接 

分 类 号：R541.7[医药卫生—心血管疾病]