养心定悸胶囊调控NOS途径改善心肌缺血再灌注损伤及其引起的心律失常

目的:明确养心定悸胶囊对心肌缺血再灌注损伤及其诱导的心律失常的保护作用及分子机制。方法:采用Langendorff离体心脏灌流系统及缺氧/复氧H9c2心肌细胞模型,考察养心定悸胶囊灌注给药对大鼠心脏左室发展压(LVDP)、左心室舒张末压(LVEDP)、左室内压上升/下降速率(±dp/dt)、心率失常相关指标,以及大鼠心肌氧化应激相关指标的影响,同时考察养心定悸胶囊含药血清对心肌细胞模型细胞活力,乳酸脱氢酶(LDH)、一氧化氮(NO)、一氧化氮合酶(eNOS,iNOS)活性及蛋白表达的影响。结果:养心定悸胶囊灌注前后均可以有效改善大鼠血流动力学,其中灌注前给药组对大鼠心脏停跳时间,心脏恢复正常律动时间及心率失常持续时间的改善作用均优于灌注后给药;养心定悸胶囊含药血清可以有效提高细胞活力,降低细胞LDH水平,升高细胞eNOS活性,降低细胞iNOS活性及NO含量,并升高磷酸化eNOS蛋白表达,抑制iNOS蛋白表达。结论:养心定悸胶囊可以有效改善心肌缺血再灌注损伤及其引起的心律失常,其作用机制与调控心肌一氧化氮合酶及NO水平相关。

Yangxin Dingji capsule improves myocardial ischemia reperfusion injury and arrhythmia by NOS pathway

OBJECTIVE To investigate the protective effect and molecular mechanism of Yangxin Dingji capsule on myocardial ischemia-reperfusion injury and arrhythmia.METHODS Langendorff isolated heart perfusion system and in vitro model of hypoxia/reoxygenation H9c2 myocardial cells were used to investigate the effect of Yangxin Dingji capsule perfusion on left ventricular pressure (LVDP), left ventricular end diastolic pressure (LVEDP), left ventricular pressure rise/fall rate (±dp/dt), arrhythmia related indicators, and myocardial oxidative stress related indicators in rats Meanwile, the effects of serum containing Yangxin Dingji capsule on cell viability, lactate dehydrogenase (LDH), carbon monoxide (NO), carbon monoxide synthase (eNOS, iNOS) activity and protein expression in myocardial cell model were also investigated. RESULTS Yangxin Dingpali capsule can improve hemodynamics of rats before and after perfusion, and the effect of Yangxin Dingpali capsule on cardiac arrest time, time to normal rhythm, and duration of arrhythmia in rats before perfusion was better than that after perfusion; Yangxin Dingpali Capsule containing drug serum can effectively improve cell viability, decrease LDH level, increase eNOS activity, decrease iNOS activity and NO content, increase phosphorylated eNOS protein expression and inhibit iNOS protein expression. CONCLUSION Yangxin Dingji capsule can effectively improve myocardial ischemia reperfusion injury and arrhythmia. Its mechanism is related to the regulation of carbon monoxide synthase and NO in myocardium.