钠离子通道1.8对急性心肌梗死后心室颤动的保护作用及机制研究

项目名称： 钠离子通道1.8对急性心肌梗死后心室颤动的保护作用及机制研究

项目编号： No.81500248

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 齐保振

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 最新研究发现，电压门控性钠离子通道1.8（NaV1.8）在心脏神经丛中表达，与急性心肌梗死患者心室颤动（室颤）发生危险降低有关，可能是室颤发生的保护性因素，但其参与室性心律失常发生的具体机制尚不清楚。我们的前期研究表明阻断心脏脂肪垫内的 NaV1.8可抑制迷走神经刺激对心脏传导及房颤诱发率的影响。而我们的预实验结果提示迷走神经刺激可延长犬的心室有效不应期，而阻断犬心脏脂肪垫内的 NaV1.8可缩短迷走神经刺激时的心室肌有效不应期，提示NaV1.8是室颤发生的保护性因素。我们提出科研假说：NaV1.8可通过调节心脏神经丛的功能及乙酰胆碱的分泌，影响心室肌的有效不应期，从而起到降低急性心肌梗死后室颤发生的保护性作用。本项目旨在揭示NaV1.8参与急性心肌梗塞后室颤发生的信号通路机制，为今后室性心律失常的治疗和新药研发提供参考。

中文关键词： 心室颤动；急性心肌梗死；钠离子通道；心脏神经丛；自主神经

英文摘要： 80% of sudden cardiac deaths are caused by ventricular tachyarrhythmias. Emerging evidences indicate that SCN10A/NaV1.8 is present in intrinsic cardiac neurons and is protective against risk of ventricular fibrillation (VF) in the setting of acute myocardial infarction, but the exact role of NaV1.8 in cardiac electrophysiology remains poorly understood. Our previous studies demonstrated that blockade of NaV1.8 channels suppresses the effects of vagus nerve stimulation (VNS) on cardiac conduction and atrial fibrillation inducibility, most likely by inhibiting the neural activity of the cardiac ganglionated plexi (GP). We also have demonstrated that VNS prolonged ventricular effective refractory period and blockade of NaV1.8 channels shortened the ventricular effective refractory period during VNS. This result indicates NaV1.8 may also play a protective role in the initiation of VF. We hypothesize that NaV1.8 can present anti-VF effect after acute myocardial infarction through regulation of the neural activity of the GP by acetylcholine, which may prolong ventricular effective refractory period. This study not only reveals a functional role for SCN10A expression in cardiac ganglionated plexi but also identifies NaV1.8 as a potential target for antiarrhythmic intervention aiming at modulating the neural control of the heart.

英文关键词： Ventricular fibrillation;acute myocardial infarction;Sodium channel;Ganglionated plexus;autonomic nervous