卡维地洛对压力负荷大鼠心功能及心肌线粒体能量代谢的保护作用

目的探讨β受体阻滞剂卡维地洛对大鼠腹主动脉缩窄术后左室肥厚及机械功能减退的预防作用是否与线粒体呼吸链酶活性的有益影响有关。方法雄性成年SD大鼠78只随机分成6组:腹主动脉缩窄组(A5指第5周时测定,A15指第15周时测定,以下同),假手术组(B5,B15),卡维地洛组(2mg/kg.d)(C5,C15),每组13只,观察术后5周及15周大鼠血流动力学参数、心室重构指标;密度梯度法分离大鼠心肌线粒体,氧电极法测定还原型烟酰胺腺嘌呤二核苷酸(NADH)氧化酶、琥珀酸氧化酶(SO)与细胞色素氧化酶(CCO)活性变化及卡维地洛的影响。结果腹主动脉缩窄术后大鼠左室质量指数增加,A15组左室压力最大上升和下降速率(±dp/dtmax)降低,卡维地洛降低左心室质量指数,增高±dp/dtmax。A5组CCO及NADH氧化酶活性均增高,卡维地洛降低二者活性。A15组NADH氧化酶、SO及CCO活性均降低,而卡维地洛增加CCO及SO活性。结论肥厚心肌线粒体呼吸链酶活性发生改变,卡维地洛改善心肌肥厚和心功能的同时,调节线粒体呼吸链酶活性从而改善心肌能量代谢。

Carvedilol Preserves Cardiac Function and Myocardial Respiratory Chain Enzyme Activities in Pressure Overload Remodeling Rats

Objective To test the hypothesis that carvedilol prevent the deterioration of mechanical function and may be related to the modulation of myocardial respiratory chain enzyme activities. Methods Male SD rats (total number:78) were randomized into 6 groups:coarctation of abdominal aorta group A(A5, A15), sham operation group B(B5, B15) and carvedilol intervention group C(C5, C15). Hemodynamics and ventriclar remodeling parameters were measured. Myocardial respiratory chain enzyme activities were measured by Clark oxygen electrodes. Results Left ventricular hypertrophy was found in A and C group. Compared with B group at week 5, the activity of cytochrome C oxidase and reduced form of nicotinamide-adenine dinucleotid (NADH) oxidase were increased significantly in A group at week 5. Compared with B group at week 15, the activity of cytochrome C oxidase, succinate oxidase and NADH oxidase were decreased as well as the dp/dtmax in A group. Carvedilol decreased activity of cytochrome C oxidase and NADH oxidase, increased activity of cytochrome C oxidase, succinate oxidase and dp/dtmax. Conclusion Myocardial respiratory chain enzyme activities was impaired in myocardium in pressure overloaded in rats. Carvedilol improved cardiac function in associated with modulation of respiratory chain enzyme activities.