卡维地洛改善大鼠肥厚心肌能量代谢及其机制

目的探讨卡维地洛对压力超负荷大鼠肥厚心肌能量代谢的影响及其机制。方法将雄性SD大鼠随机分为假手术组、腹主动脉缩窄组和卡维地洛治疗组,15周后观察大鼠血流动力学参数、心室重构指标。采用密度梯度法提取大鼠心肌线粒体,用抑制剂终止法测定线粒体腺苷酸转运体（adenine nucleotide translocator,ANT）的转运活性,高效液相色谱法测量心肌组织及线粒体内腺苷酸含量。结果大鼠腹主动脉缩窄术后15周出现左心室肥厚及心功能减退;组织及线粒体内ATP、ADP及（ATP+ADP）含量及ANT转运活性降低。卡维地洛减轻心室肥厚、改善心功能的同时,增加组织及心肌线粒体腺苷酸含量,增强ANT转运活性。结论肥厚心肌心功能减退,心肌线粒体腺苷酸含量及ANT活性降低,使能量的产生和利用异常。卡维地洛改善心肌肥厚和心功能,且可能通过增强ANT活性而促进线粒体内产能,从而改善心肌能量代谢。

Effect of Carvedilol on energy metabolism of left ventricular hypertrophy induced by pressure overload in rats and its mechanism

AIM To study the effect of Carvedilol on the energy metabolism of left ventricular hypertrophy induced by pressure overload in rats and its mechanism.METHODS Male SD rats were randomized into 3 groups: coarctation of abdominal aorta group(CA group),sham operation group(SH group) and Carvedilol intervention group(CI group).The hemodynamics and ventricular remodeling parameters were measured.Mitochondria were isolated by centrifugation.The size of adenine acid pool(ATP,ADP,AMP) in myocardium and mitochondria was measured by high performance liquid chromatography(HPLC) and the ANT activity was detected by atractyloside-inhibitor stop technique.RESULTS Compared with that in sham operation group,the content of ATP,ADP and(ATP ADP) in myocardium and mitochondria decreased significantly in CA group,and an reduction of ANT activity was observed.Carvedilol increased the content of adenine acid pool and improved the activity of ANT.CONCLUSION Myocardial high energy phosphates content and ANT activity decrease in rats with left ventricular hypertrophy.Carvedilol treatment improves left ventricular hypertrophy and cardiac dysfunction and increases high energy phosphates content in myocardium and mitochondria,thus improving the myocardial metabolism.