去肾神经术(RD)对比药物治疗急性心梗(AMI)后心衰(HF)大鼠的疗效及机制

 目的 通过对比分析去肾神经术（renal denervation，RD）和药物治疗对急性心肌梗死（acute myocardial infarction，AMI）后心力衰竭（heart failure，HF）大鼠模型心功能、肾素-血管紧张素-醛固酮系统、交感神经系统和心脏自主神经系统的影响，探究RD与抗HF药物的疗效差异、最佳治疗时机以及疗效机制。方法 140只雄性Wistar大鼠，随机分为对照组、AMI组（心肌梗死组）、RD组（去肾神经组）、MI-1d+RD组（AMI后1天行RD）、MI-1d+Drugs组（AMI后1天予以药物治疗）、MI-4w+RD组（AMI后4周行RD）、MI-4w+Drugs组（AMI后4周予以药物治疗），每组各20只。AMI后1天及4周后分别行RD、β受体阻滞剂（β-blocker）+血管紧张素受体拮抗剂（ACEI）药物联合治疗。检测并记录AMI后8周各组大鼠模型的心功能、血浆脑钠尿肽（brain natriuretic peptide，BNP）、肾素、血管紧张素Ⅱ（Ang Ⅱ）、醛固酮（aldosterone，ALD）、去甲肾上腺素（norepinephrine，NE）水平，梗死心肌NE含量，心率和5 min内NN间期标准差（standard deviation of NN intervals，SDNN）。结果 AMI后8周，对照组、AMI组、RD组、MI-1d+RD组、MI-1d+Drugs组、MI-4w+RD组、MI-4w+Drugs组大鼠的左心室射血分数（left ventricular ejection fraction，LVEF）分别为85%、36%、82%、77%、65%、53%、45%。AMI组大鼠较对照组LVEF显著下降（P<0.05），血浆BNP、肾素、Ang Ⅱ、ALD、NE水平均显著增加（P<0.05），梗死心肌NE水平、HR显下降（P<0.05），SDNN显著增加（P<0.05）。MI-1d+RD组大鼠较AMI及MI-1d+Drugs组LVEF显著增加（P<0.05），血浆BNP、肾素、Ang Ⅱ、ALD、NE水平均显著下降（P<0.05）。MI-1d+RD组、MI-1d+Drugs组大鼠较AMI组梗死心肌NE含量、心率显著均增加（P<0.05），SDNN显著下降（P<0.05）；MI-4w+RD组、MI-4w+Drugs组大鼠较AMI组梗死心肌NE、心率及SDNN差异均无统计学意义（P>0.05）。结论 AMI后早期行RD改善心功能的疗效强于β受体阻滞剂与血管紧张素转化酶抑制剂联合治疗，其疗效机制包括抑制交感神经系统、肾素-血管紧张素-醛固酮系统活性以及调节心脏交感-迷走神经功能平衡。

The efficacy and mechanism of renal denervation (RD) versus drugs in treating post-acute myocardial infarction (AMI) heart failure (HF) in rats

Objective To compare the effects of renal denervation (RD) and drug therapy on cardiac function,renin-angiotensin-aldosterone system,sympathetic nervous system and cardiac autonomic nervous system in rats with post-acute myocardial infarction (AMI) heart failure and to explore the appropriate time for RD treatment and it's therapeutic mechanism. Methods One hundred and forty Wistar rats were randomly divided into control group,AMI group,RD group,MI-1d+RD group,MI-1d+Drugs group,MI-4w+RD group and MI-4w+Drugs group (20 in each group).RD and drug therapy (β-blocker combined angiotensin converting enzyme inhibitors) was applied one day and 4 weeks after AMI separately.The cardiac function,brain natriuretic peptide (BNP),plasma renin,angiotensin Ⅱ,aldosterone (ALD),norepinephrine (NE),infarcted myocardium norepinephrine content,heart rate (HR) and standard deviation of NN interval within 5 minutes (SDNN) were measured and recorded in each group 8 weeks post AMI. Results On the eighth week after AMI,left ventricular ejection fraction (LVEF) in control group,AMI group,RD group,MI-1d+RD group,MI-1d+Drugs group,MI-4w+RD group and MI-4w+Drugs group was 85%,36%,82%,77%,65%,53%,45% respectively.Compared with the control group,AMI group showed a significant decrease in LVEF,infarcted myocardium NE content and HR (P<0.05),and a significant increase in plasma BNP,renin,angiotensin Ⅱ,ALD,NE and SDNN (P<0.05).Compared with MI and MI-1d+Drugs groups,LVEF in MI-1d+RD group increased significantly (P<0.05),while the plasma BNP,renin,angiotensin Ⅱ,ALD and NE decreased significantly (P<0.05).Compared with AMI group,MI-1d+RD group and MI-1d+Drugs group showed a significant increase in infarcted myocardium NE content and HR (P<0.05),and a significant decrease in SDNN (P<0.05),while MI-4w+RD group and MI-4w+Drugs group showed no significant difference in NE,HR and SDNN (P>0.05). Conclusions The efficacy of early RD intervention in improving cardiac function after AMI is better than that of combination therapy of beta-blocker and angiotensin converting enzyme inhibitors.Its therapeutic mechanisms include inhibition of the sympathetic nervous system,renin-angiotensin-aldosterone system activity,and regulation of cardiac sympathetic-vagal balance.