右美托咪定抗缺血性心律失常作用及机制研究  

Effect and mechanism of dexmedetomidine on ischemic arrhythmia

作　　者：郭悦平 刘艳 刘颖 于佳岐 王超 周杨[5] 张海莹 GUO Yue-ping;LIU Yan;LIU Ying;YU Jia-qi;WANG Chao;ZHOU Yang;ZHANG Hai-ying(Hainan Medical University First Affiliated Hospital of Department of Anesthesiology,Haikou 570102,China;Key Laboratory of Tropical Translational Medicine of Ministry of Education,College of Pharmaceutical,Hainan Medical University,Haikou 571199,China;The First Clinical College of Hainan Medical University,Haikou 570102,China;Sanya Central Hospital,Sanya 572000,Hainan,China;Department of Pharmacology,Harbin Medical University,Harbin 150081,China)

机构地区：[1]海南医学院附属第一医院麻醉科,海南海口570102 [2]海南医学院药学院、海南医学院热带转化医学教育部重点实验室,海南海口571199 [3]海南医学院第一临床学院,海南海口571199 [4]三亚中心医院,海南三亚572000 [5]哈尔滨医科大学药理教研室,黑龙江哈尔滨150081

出　　处：《海南医学院学报》2021年第21期1607-1612,共6页Journal of Hainan Medical University

基　　金：海南省高层次人才基金项目(2019RC376,2019RC225)。

摘　　要：目的:利用体外细胞分子生物学实验探讨心肌α2受体激动剂右美托咪定抗心律失常的作用及机制。方法:将50只Wistar大鼠采用数字随机法分为5组(n=10):假手术组(Ctl组)、心律失常模型组(Model组)、心律失常+右美托咪定组(Dex组)、心律失常+育亨宾+右美托咪定组(Yoh+Dex组)、心律失常+育亨宾组(Yoh组)。Ctl组穿线不结扎左冠状动脉前降支,Model组结扎左冠状动脉前降支,Dex组、Yoh+Dex组、Yoh组,分别尾静脉注射给药后,结扎左冠状动脉前降支。术后利用BL-420E系统记录心电图;采用Curtis和Walker心率失常评分法对心率失常严重程度进行定量分析;根据各组大鼠寿命进行生存分析;造模完成21 d后TTC染色测量心肌梗死面积;急性分离大鼠心肌细胞,降低细胞外液pH值模拟心肌缺血,膜片钳技术检测心肌细胞动作电位时程。结果:与Ctl组比较,Model组心律失常评分和心肌梗死面积增加(P<0.05),QTc间期延长;与Model组和Yoh组比较,Dex组的大鼠心律失常评分降低(P<0.001),死亡率、心肌梗死面积均明显降低(P<0.05);右美托咪定缩短QTc间期(P<0.01)、APD_(50)、APD_(90)(P<0.05),α2受体阻断剂育亨宾抑制了右美托咪定的作用。结论:右美托咪定通过激动心肌α2受体,影响动作电位复极过程,防治缺血诱发的室性心律失常。Objective:To explore the antiarrhythmic effect and mechanism of dexmedetomidine,a myocardialα2 receptor agonist in vitro.Methods:Fifty Wistar rats were randomly divided into five groups(n=10):sham operation group(Ctl),arrhythmia model group(Model),arrhythmia+dexmedetomidine group(Dex),arrhythmia+yohimbine+dexmedetomidine group(Yoh+Dex),arrhythmia+yohimbine group(Yoh).The Ctl group just thread left anterior descending coronary artery without ligation.Model group recorded 10 minutes of normal ECG,ligated the left anterior descending coronary artery,and continued to record the ECG for 2 hours.Dex group,Yoh+Dex group and Yoh group were ligated left anterior descending coronary artery after administration.Use BL-420E system to record ECG;Curtis and Walker arrhythmia scores were used to analyze the severity of arrhythmia;perform survival analysis according to the life span of each group of rats;after 21 days of modeling,measure the area of myocardial infarction by TTC staining.The pH value of extracellular fluid was decreased to simulate myocardial ischemia.Patch clamp technique was used to detect the action potential duration of myocardial cells.Results:Compared with the Ctl group,the arrhythmia score and myocardial infarction area in the Model group was increased(P<0.05),the mortality and myocardial infarction area were alsosignificantly reduced(P<0.05).Compared with Model group and Yoh group,the arrhythmia score of Dex group was significantly lower(P<0.001),the mortality and myocardial infarction area were significantly lower(P<0.05);Dexmedetomidine shortened QTc interval(P<0.01),APD_(50) and APD_(90)(P<0.05).Theα2 receptor blocker Yohimbine inhibited the effect of dexmedetomidine.Conclusion:Dexmedetomidine affects the action potential repolarization process by stimulating myocardialα2 receptors,and prevents ischemia-induced ventricular arrhythmia.

关 键 词：右美托咪定 α_(2)受体 心律失常 动作电位时程 

分 类 号：R614[医药卫生—麻醉学]