胰高血糖素样肽― 1受体激动剂Exendin―4在大鼠缺血性室性心律失常中作用.docVIP

胰高血糖素样肽― 1受体激动剂Exendin―4在大鼠缺血性室性心律失常中作用 　　摘要：目的 探究胰高血糖素样肽- 1（GLP -1）受体激动剂Exendin-4（Ex-4）在大鼠缺血性室性心律失常中的作用及机制。方法 40只雄性SD大鼠随机分为4组。缺血组（MI）；Ex-4+缺血组（MI + Ex-4）； 5-羟基葵酸+ Ex-4+缺血组（MI-Ex-4-5-HD）；5-羟基葵酸+缺血组（MI-5-HD）。各组在制作MI模型前分别给予生理盐水、Ex-4+5-HD、5-HD预处理。持续心电监护，观察缺血30 min内各组室性心动过速（VT）和心室颤动（VF）发生率、VT+VF持续时间、发生次数和室性心律失常的严重程度。结果 Ex-4显著减少大鼠心肌缺血30 min发生率（P0.05）；与心肌缺血组比较，Ex-4可以有效减少室速+室颤的持续时间、发生次数和心律失常的严重程度有关（P0.05）；5-HD可以有效消除Ex-4减少室速+室颤的持续时间、发生次数和心律失常的严重程度有关（P0.05）。结论 胰高血糖素样肽- 1受体激动剂Ex-4有效减轻大鼠缺血性室性心律失常，而这一保护作用可能与线粒体KATP通道的信号转导相关。 　　关键词：室性心律失常；心肌梗死；Exendin-4；线粒体ATP敏感性钾离子 　　中图分类号：R541.7 R285.5 文献标识码：A 　　doi：10.3969/j.issn.1672-1349.2014.09.040 文章编号：1672-1349（2014）09-1109-03 　　Glucagon-like Peptide-1 Receptor Agonist Exendin-4 　　Attenuates Ischemia-induced Ventricular Arrhythmias in Rats 　　Zhang Kai，Peng Biwen 　　Central Hospital of Huangshi（Huangshi 435000）；School of Basic Medical Sciences，Wuhan University （Wuhan 430071） 　　Abstract：Objective To investigate whether glucagon-like peptide-1（GLP-1） and its receptor agonist exendin-4 （Ex-4） could provide benefi cial effects for ischemia-induced ventricular arrhythmias in rats.Methods Forty SD male rats （250 g to 300 g） were randomly divided into four groups：Myocardial infarct group （MI group，n=10），myocardial ischemia plus Ex-4 group （MI+Ex-4 group，n=10），myocardial ischemia plus Ex-4 plus 5-hydroxydecanoic acid group （MI+Ex-4+5-HD group，n=10），myocardial ischemia plus 5-hydroxydecanoic acid group （MI+5-HD group，n=10）.During 30-minute ischemia，the incidence of ventricular tachycardia （VT） and ventricular fibrillation （VF），duration of VT+VF，number of VT+VF，and severity of arrhythmias were monitored and analyzed.Results During the 30 minute ischemia，Ex-4 significantly reduced the incidence of VF （P0.05）.The duration of VT+VF，the number of VT+VF episodes，and the severity of arrhythmias were all significantly reduced by Ex-4 compared to those in MI group （P0.05 for all）.Administration of 5-HD abolished the protective effects of Ex-4 on V