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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 the protein kinase C agonist phorbol ester (PMA) on ventricular arrhythmia in rabbits and to explore its mechanism. Methods: Left ventricular wedge myocardial perfusion model was prepared and randomly divided into normal control group (perfusion Tyrode’s solution), PMA group (perfusion Tyrode’s solution + PMA500nmol / L). Using floating glass microelectrode method to synchronously record the transmembrane action potentials and transmural electrocardiograms of endocardial and epicardial cardiomyocytes, and to induce the occurrence of ventricular tachycardia induced by programmed pre-stimulation. The total amount of connexin 43 (Cx43) and the level of S368 dephosphorylated (NP-Cx43S368) protein in cardiomyocytes were detected by Western blot. Results: Compared with the normal control group, QT interval in PMA group was significantly shorter than that in control group [(260 ± 25) ms: (302 ± 21) ms, P <0.01] (61 ± 13) ms: (51 ± 7) ms, 0.24 ± 0.05: 0.17 ± 0.02, all P <0.01]. The total amount of Cx43, NP-Cx43S368 protein (P <0.05, P <0.01, respectively). Compared with the normal control group, PMA group significantly increased the incidence of ventricular tachycardia (70.0% vs 0%, P <0.05). Conclusion: PMA leads to arrhythmia by down-regulating the total amount and function of myocardial gap junction.