右美托咪定对心肌缺血-再灌注过程中单相动作电位振幅的影响及其与心肌损伤的相关性

Effect of dexmedetomidine on monophasic action potential amplitude in myocardial ischemiareperfusion and its correlation with myocardial injury

目的:研究右美托咪定对心肌缺血-再灌注过程中单相动作电位振幅(MAPA)的影响及其与心肌损伤的相关性。方法:选择SD大鼠作为实验动物并随机分为对照组、缺血再灌注组(I/R组)、右美托咪定组(Dex组),I/R组和Dex组建立心肌缺血再灌注损伤模型,Dex组同时给予右美托咪定干预;在Langendorff灌流系统内测定心肌内膜层、中膜层、外膜层的MAPA;另取心肌组织并测定氧化应激分子含量及凋亡基因表达量。结果:I/R组心肌组织内膜层、中膜层、外膜层MAPA的水平以及心肌组织中Klotho、SOD的含量均显著低于对照组,心肌组织中CaMKⅡ、NOX2、NOX4、MDA的含量以及CaSR、USP14、JNK、Bax、Fas、Caspase-3的mRNA表达量显著高于对照组;Dex组心肌组织内膜层、中膜层、外膜层MAPA的水平以及心肌组织中Klotho、SOD的含量均显著高于I/R组,心肌组织中CaMKⅡ、NOX2、NOX4、MDA的含量以及CaSR、USP14、JNK、Bax、Fas、Caspase-3的mRNA表达量显著低于I/R组;Pearson检验显示:心肌组织内膜层、中膜层、外膜层MAPA的水平与心肌组织中CaMKⅡ、NOX2、NOX4、MDA的含量以及CaSR、USP14、JNK、Bax、Fas、Caspase-3的mRNA表达量呈负相关,与Klotho、SOD的含量呈正相关。结论:右美托咪定能够增加心肌缺血-再灌注过程中的MAPA且与氧化应激反应、细胞凋亡的抑制密切相关。

Objective：To study the effect of dexmedetomidine on monophasic action potential amplitude（MAPA）in myocardial ischemia-reperfusion and its correlation with myocardial injury.Methods：SD rats were selected as the experimental animals and randomly divided into control group,ischemia reperfusion group（I/R group）and dexmedetomidine group（Dex group）,I/R group and Dex group were made into myocardial ischemia-reperfusion injury models,and Dex group were given exmedetomidine intervention;the MAPA of myocardial tunica intima layer,tunica media layer and tunica externa layer were measured in Langendorff perfusion system;myocardial tissue was collected to determine the contents of oxidative stress molecules and the expression of apoptosis genes.Results：The MAPA levels of myocardial tunica intima layer,tunica media layer and tunica externa layer as well as Klotho and SOD contents in myocardial tissue of I/R group were significantly lower than those of control group whereas CaMKⅡ,NOX2,NOX4 and MDA contents as well as CaSR,USP14,JNK,Bax,Fas and Caspase-3 mRNA expression in myocardial tissue were significantly higher than those of control group;the MAPA levels of myocardial tunica intima layer,tunica media layer and tunica externa layer as well as Klotho and SOD contents in myocardial tissue of Dex group were significantly higher than those of I/R group whereas CaMKⅡ,NOX2,NOX4 and MDA contents as well as CaSR,USP14,JNK,Bax,Fas and Caspase-3 mRNA expression in myocardial tissue were significantly lower than those of I/R group;Pearson test showed that the MAPA levels of myocardial tunica intima layer,tunica media layer and tunica externa layer were negatively correlated with CaMKⅡ,NOX2,NOX4 and MDA contents as well as CaSR,USP14,JNK,Bax,Fas and Caspase-3 mRNA expression in myocardial tissue,and positively correlated with Klotho and SOD contents.Conclusion：Dexmedetomidine can increase the MAPA in myocardial ischemia-reperfusion process,and is closely related to the inhibition of oxidative stress response and apoptosis.