肾动脉去交感神经术对大鼠急性心肌梗死后室性心律失常的影响及相关机制的研究

Effects of renal denervation on ventricular arrhythmia after acute myocardial infarction in rats and the related mechanisms

目的研究肾动脉去交感神经术(RDN)对急性心肌梗死(AMI)后室性心律失常的影响及作用机制。方法采用大鼠心肌梗死模型,将24只Sprague-Dawley(SD)大鼠分为4个组,对照组(Control组)、AMI组、RDN-1d+AMI组和RDN-2w+AMI组,按分组对SD大鼠进行RDN干预,饲养不同时间后建立AMI模型,术后即可采用PowerLab多导心电监护仪连续描记,监测RDN对室性心律失常发生的抑制作用。观察1 h后,留取心脏组织,采用TH染色检测心脏交感神经活性。Western blot检测心肌梗死区各种离子通道蛋白的表达。用Power Lab/8SP生物信息采集仪检测肾脏交感神经活动情况。结果与AMI组比较,RDN-1d+AMI组和RDN-2w+AMI组室性心动过速发生次数减少,差异有统计学意义(P<0.01),其中RDN-1d组减少次数更明显。与Control组肾脏交感神经放电情况比较,RDN-1d组和RDN-2w组下降,差异有统计学意义(P<0.01),其中RDN-1d组效果更明显。TH染色提示RDN能够抑制AMI后心脏局部交感神经的活性。与Control组相比,AMI组Nav1.5、Cav1.2和Kir2.1蛋白表达下调,而与AMI组相比,RDN-2w+AMI组可抑制Nav1.5、Cav1.2和Kir2.1蛋白表达的下调,而RDN-1d+AMI组不能抑制上述蛋白表达的下调。结论RDN能有效的减少AMI后室性心律失常的发生,早期主要通过抑制肾脏交感神经放电,后期通过抑制肾脏交感神经放电和离子通道蛋白上调发挥作用。

Objective To investigate the effects of renal denervation(RDN)on ventricular arrhythmia after acute myocardial infarction(AMI)and its mechanism.Methods Using a rat myocardial infarction model,24 Sprague-Dawley(SD)rats were divided into four groups:the control group(Control),the AMI group,the RDN-1d+AMI group and the RDN-2w+AMI group.The SD rats were subjected to RDN intervention,and the AMI model was established after feeding for different times.PowerLab multi-channel ECG monitor was continuously recorded after surgery to monitor the inhibitory effect of RDN on the occurrence of ventricular arrhythmia.After 1 h of observation,the heart tissue was collected,and TH staining was used to detect cardiac sympathetic nerve activity.Western blot was used to detect the expression of various ion channel proteins in the myocardial infarction area.Renal sympathetic nerve activity was detected by Power Lab/8SP biological information acquisition instrument.Results Compared with the AMI group,the frequency of ventricular tachycardia in the RDN-1d+AMI group and RDN-2w+AMI group reduced,the difference was statistically significant(P<0.01),and the decrease in the RDN-1d group was more obvious.Compared with the sympathetic nerve discharge in the Control group,the RDN-1d group and the RDN-2w group decreased,the difference was statistically significant(P<0.01),and the RDN-1d group was more effective.TH staining suggested that RDN could inhibit local sympathetic nerve activity after AMI.Compared with the control group,the protein expressions of Nav1.5,Cav1.2 and Kir2.1 in the AMI group were down-regulated,while compared with the AMI group,the RDN-2w+AMI group could inhibit the down-regulation of Nav1.5,Cav1.2 and Kir2.1 protein expression,while the RDN-1d+AMI group could not inhibit the down-regulation of protein expression.Conclusion RDN can effectively reduce the occurrence of ventricular arrhythmias after AMI.In the early stage,it mainly inhibits renal sympathetic nerve discharge,and later inhibits renal sympathetic discharge and ion channel protein upregulation.