艾塞那肽对心肌梗死后心力衰竭大鼠心电生理的影响及其机制研究

Effect of glucagon-like peptide-1 receptor agonist exendin-4 on electrophysiology in myocardial infarction-heart failure rats and the mechanism

目的探讨胰高血糖素样肽-1受体（GLP-1R）激动剂艾塞那肽（exendin-4，Ex-4）对心肌梗死（心梗）后心力衰竭（心衰）大鼠心电生理的影响及其可能的机制。方法将48只雄性SD大鼠按照随机数字表法随机分为假手术组、心梗组、心梗＋Ex-4组、心梗＋Ex-4＋Ex-9-39组，每组12只。通过结扎冠状动脉前降支建立心肌梗死模型。术后4周进行超声心动图检查，并植入心电记录器，观察24 h室性心律失常的发生情况。在Langerdorff灌流下，记录心肌梗死周边区单向动作电位（AP）和室性心律失常的诱发率。通过Western blotting检测心梗周边区钙循环相关蛋白的表达。结果与心梗组相比，心梗＋Ex-4组术后4周心功能改善、24 h室性心律失常发生明显减少、Burst刺激下室性心律失常诱发率显著下降（P〈0.05）。同时，与心梗组相比，心梗＋Ex-4组SERCA2a、p-PLB、Cav1.2表达增加，p-RyR表达下降（P〈0.05）。Ex9-39抑制了Ex-4的保护作用（P〈0.05）。结论GLP-1R激动剂Ex-4改善心梗后电重构可能与调节钙循环蛋白表达有关。

ObjectiveTo investigate the effect of glucagon-like peptide-1 receptor （GLP-1R） agonist exendin-4 on electrophysiology in myocardial infarction-heart failure rats and mechanism.MethodsForty-eight male Sprague-Dawley rats were randomly divided into sham group, myocardial infarction （MI） group, MI＋Ex-4 group, MI＋Ex-4＋Ex9-39 group. The methods of creating MI was ligation of left anterior descending coronary artery. Echocardiographic measurements were assessed four weeks after MI surgery and telemetry probe was implanted in the abdominal cavity of rats to record heart signals in conscious. The monophasic action potential and the induction ratio of ventricular arrhythmia were assessed in MI border zone in langendorff-perfused hearts. The expression of calcium handling proteins was detected by western blotting method.ResultsCompared with MI group, cardiac function was improved, ventricular arrhythmia was decreased in ambulatory ECG recording and the incidence of Burst-pacing induced ventricular arrhythmia was decreased in MI＋Ex-4 group （P〈0.05） . Meanwhile, the expression of sarco-endoplasmic reticulum ATPase 2a （SERCA2a） , phosphorylated phospholamban （p-PLB） , Cav1.2 were increased, and the expression of phosphorylated ryanodine receptor 2 （RyR2） was decreased in MI＋Ex-4 group （P〈0.05） . Exendin9-39 abolished the effects of exedin-4 （P〈0.05） .ConclusionGLP-1R agonist exendin-4 ameliorates electrical remodeling which may associated with the effects of stabilization of calcium handling proteins.