美托洛尔对缺血糖尿病大鼠心肌的电生理作用

Effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats

目的:研究美托洛尔对糖尿病大鼠心肌缺血缺氧的电生理作用及其机制。方法:雄性Sprague-Dawley(SD)大鼠40只,实验分为:糖尿病组、糖尿病+左交感神经切除组、糖尿病+美托洛尔组,空白对照组,每组10只大鼠。通过腹腔注射链脲佐菌素(60 mg/kg)建立糖尿病模型,模型建立后行离体的心脏的电生理研究。分别测定心室舒张期兴奋阈(Diastolic effective threshold,DET),心室有效不应期(Effective refractive period,ERP),心室颤动阈(Ventricular fibrillationthreshold,VFT),并测定各组的血清神经生长因子(nerve growth factor,NGF)浓度。结果:美托洛尔可以提高糖尿病大鼠心肌缺血后的DET,交感神经切除组可以明显提高糖尿病大鼠的VFT,具有统计学差异。美托洛尔组的VFT比糖尿病大鼠的VFT明显升高,心肌缺血前,美托洛尔组的VFT和糖尿病组的VFT比较并没有差异。缺血后,美托洛尔组的VFT比糖尿病大鼠的VFT明显升高,糖尿病组及糖尿病+美托洛尔组大鼠其NGF浓度明显高于对照组,具有统计学差异;而糖尿病+交感神经切除组大鼠,其NGF浓度与对照组间差异没有显著性。结论:交感神经的重构对糖尿病大鼠心肌的电生理,特别是对缺血后的电生理的影响发生起到重要的作用,美托洛尔可以提高缺血后糖尿病大鼠的VFT,降低心肌的兴奋阈值,从而可能降低室性心律失常的发生。其机制可能与其抑制交感神经的重构有关。

Objective: To investigate the effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats. Methods: Forty Sprague-Dawley(SD) rats were divided into 4 groups:diabetes group;diabetes and ablation of left sympathetic nerve group;diabetes and metoprolol group and sham group.The diabetes model was induced by intraperitoneal injection of streptozotocin(STZ,60 mg/kg).The ventricular diastolic effective threshold(DET),effective refractive period(ERP),and Ventricular fibrillation threshold(VFT) were measured.The serum concentration of nerve growth factor(NGF) was measured. Results: Metoprolol increased DET of ischemic and anoxic myocardium in diabetic rats.The ablation of the left sympathetic nerve increased VFT of diabetic rats.VFT in metoprolo group was significantly increased compared to diabetes group after ischemia.The concentrations of NGF in diabetic group and metoprolol group were higher than those in sham group.There were no difference in NGF levels between ablation of left sympathetic nerve group and sham group. Conclusions: The remodeling of sympathetic nerve affects the electrophysiology of ischemic myocardium of diabetic rats.Metoprolol can increase the VFT and decrease the excitation threshold of the ischemic myocardium in diabetic rats.