下调左侧星状神经节神经元M通道对大鼠急性心肌梗死后室性心律失常的影响  

Effect of downregulation of the M-channel in left stellate ganglion neurons on ventricular arrhythmia after acute myocardial infarction in rats

作　　者：彭锦强 周明敏[1] 徐辽 黄迪哲 王冬雨 刘育[1] PENG Jinqiang;ZHOU Mingmin;XU Liao;HUANG Dizhe;WANG Dongyu;LIU Yu(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所心血管病湖北省重点实验室,武汉430060

出　　处：《中国心脏起搏与心电生理杂志》2025年第1期48-53,共6页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然科学基金面上项目(82270318)。

摘　　要：目的观察下调左侧星状神经节(LSG)神经元M通道对大鼠急性心肌梗死(AMI)后室性心律失常的影响。方法32只大鼠随机分为4组(每组8只):假手术组(sham组)、急性心肌梗死组(AMI组)、KCNQ2下调组(shKCNQ2组)和病毒对照组(shCtrl组)。除sham组外,其余3组均通过结扎冠状动脉(简称冠脉)左前降支建立AMI模型。shKCNQ2组和shCtrl组在建模前3周分别在LSG内显微注射AAV2-GFP-U6-KCNQ2-shRNA(沉默KCNQ2)或AAV2-GFP-U6-Scrmb-shRNA。观察冠脉结扎后20 min内室性心律失常发生情况。于冠脉结扎后第3周分析心率变异性(HRV)频域指标:高频(HF)和低频(LF),于冠脉结扎后第4周测量心室电生理参数。结果AMI组、shKCNQ2组和shCtrl组各有1只、4只和2只大鼠在结扎冠脉后因心室颤动死亡,后分别补充相应数量大鼠完成实验。与sham组相比,AMI组和shCtrl组室性心律失常发生次数、室性心动过速持续时间和室性心律失常评分均显著升高(P均<0.05),HRV频域指标HF明显降低(P<0.05)、LF和LF/HF比值显著升高(P<0.05),梗死周边区心室有效不应期明显增加(P<0.05),动作电位(APD)复极90%的时间(APD90)及诱发APD交替的最大起搏周期长度显著延长(P均<0.05),心室颤动阈值明显降低(P<0.01)。与AMI组和shCtrl组相比,shKCNQ2组以上指标均显著恶化(P均<0.05)。结论下调LSG神经元M通道的表达增加心脏交感神经活性,加重心室电生理不稳定性,促进室性心律失常的发生。Objective To investigate the effects of M-channel deficiency in left stellate ganglion(LSG)neurons on ventricular arrhythmias following acute myocardial infarction(AMI)in rats.Methods Thirty-two Sprague-Dawley rats were randomly divided into four groups(n=8per group):sham operation group(sham),AMI model group(AMI),adeno-associated virus intervention group(shKCNQ2),and virus control group(shCtrl).Except for the sham group,the AMI model was induced in the other three groups by ligating the left anterior descending coronary artery.Three weeks before modeling,the shKCNQ2and shCtrl groups received LSG microinjections of AAV2-GFP-U6-KCNQ2-shRNA(for KCNQ2silencing)or AAV2-GFP-U6-Scrmb-shRNA,respectively.Ventricular arrhythmias were observed within 20minutes after coronary ligation.Heart rate variability(HRV)frequency-domain parameters,including high-frequency(HF)and low-frequency(LF)components,were analyzed at three weeks after coronary artery ligation.Ventricular electrophysiological parameters were measured four weeks after coronary artery ligation.Results In the AMI,shKCNQ2,and shCtrl groups,one,four,and two rats,respectively,died from ventricular fibrillation(VF)after coronary ligaiton;these were replaced to complete the experiment.Compared with the sham group,the AMI and shCtrl groups showed significant increases in the frequency of ventricular arrhythmias,duration of ventricular tachycardia,and ventricular arrhythmia scores(all P<0.05).The HRV frequency domain indicator HF was significantly reduced(P<0.05),whereas the LF and LF/HF ratio were significantly increased(P<0.05).The effective refractory period of the infarcted border zone increased significantly(P<0.05).The action potential duration(APD)at 90%repolarization(APD90)and the maximum pacing cycle length inducing APD alternans were significantly prolonged(P<0.05),and the VF threshold was significantly reduced(P<0.01).Compared to the AMI and shCtrl groups,all these indices were significantly worsened in the sh-KCNQ2group(all P<0.05).Conclusion Downregulation o

关 键 词：急性心肌梗死 室性心律失常 左侧星状神经节 M通道 KCNQ2亚基 

分 类 号：R542.22[医药卫生—心血管疾病] R541.7[医药卫生—内科学]