Objective To study the role of calmodulin kinase Ⅱ and protein kinase A signal transduction pathway in the catecholaminergic polymorphic ventricular tachycardia(CPVT). Methods Japanese rabbits were randomly divided into control group,model group,KN93 group,and H89 group. Arterially perfused rabbit left ventricular wedge models were prepared. The control group was perfused with Tyrode's solution and the model group with caffeine+isoproterenol to mimic the CPVT. The KN93 group was perfused with KN93 + caffeine+isoproterenol, and H89 group with H89+caffeine+isoproterenol. The triggered activity(TA)and ventricular arrhythmias were observed after program stimulation. Results The incidence of TA and ventricular tachycardia in control group was 0. After perfusion with caffeine+isoproterenol,the QT interval was decreased. The incidence of TA and ventricular tachycardia in model group was 12/13 and 8/13 respectively. After treatment with KN93 or H89,the incidence of TA was decreased to 4/9 and 6/11 ,and the incidence of ventricular arrhythmia reduced to 1/9 and 2/11. Calmodulin kinase Ⅱ inhibitors and protein kinase A inhibitor could reduce the triggered activity and ventricular arrhythmia in the CPVT model. Conclusion Calmodulin kinase Ⅱ and protein kinase A signal transduction pathway play an important role in the catecholaminergic polymorphic ventricular tachycardia. The signal transduction pathway may become the therapeutic targets for CPVT.%目的 研究钙调蛋白激酶Ⅱ和蛋白激酶A信号转导通路在儿茶酚胺敏感性室性心动过速中的作用.方法 日本长耳白兔随机分成正常对照组、模型组、KN93组以及H89组.制备兔左室楔形心肌块灌流模型,正常组灌流蒂罗德液,模型组灌流咖啡因和异丙肾上腺素,KN93组在灌流咖啡因与异丙肾上腺素的基础上加灌KN93,H89组同样在灌流咖啡因与异丙肾上腺素的基础上加灌H89.观察通过程序性刺激后触发活动和室性心律失常的诱发情况.结果 对照组触发活动和室性心律失常的诱发率为0.通过灌流咖啡因与异丙肾上腺素以后,QT间期明显缩短,模型组触发活动的诱发率为12/13,室性心律失常的发生率为8/13;而灌流KN93和H89后触发活动分别减少至4/9和6/11,室性心律失常减少到1/9和2/11.钙调蛋白激酶Ⅱ抑制剂和蛋白激酶A抑制剂可以减少药物灌流儿茶酚胺敏感性室速模型的触发活动和室性心律失常的发生.结论 儿茶酚胺敏感性室性心动过速的发生跟钙调蛋白激酶Ⅱ和蛋白激酶A信号转导通路密切相关.该信号通路有望成为儿茶酚胺敏感性室性心动过速的治疗靶点.
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