阿托伐他汀通过调节钠-钙交换体改善心力衰竭大鼠心脏功能

Effect of atorvastatin on progression of heart failure and association with sodium-calcium exchanger expression

目的:探讨阿托伐他汀对心力衰竭大鼠心脏功能及心肌细胞钠-钙交换体表达的影响。方法:结扎大鼠冠状动脉左前降支8周,制备心肌梗死后心力衰竭模型。随机分3组,即假手术组、心力衰竭组与阿托伐他汀治疗组,分别于结扎后第2天给予安慰剂或阿托伐他汀治疗。8周后测定大鼠心脏功能及钠-钙交换体蛋白表达水平。培养原代乳鼠心肌细胞,通过缺氧模型分析阿托伐他汀对细胞内钙水平的影响。结果:阿托伐他汀治疗组较心衰组BNP水平降低,左室舒张末内径缩小,左室短轴缩短率升高。阿托伐他汀治疗明显降低心力衰竭时钠-钙交换体蛋白表达量,抑制缺氧诱导细胞内钙水平增加。结论:阿托伐他汀治疗改善心功能,可能与影响心力衰竭心肌细胞钠-钙交换体的表达及功能有关。

AIM：To investigate the effect of atorvastatin on the development of heart failure after myocardial infarction and the association with sodiumcalcium exchanger （NCX） expression.METHODS：The model of heart failure was established by ligation of the anterior descending coronary artery for 8 weeks.The rats were randomly divided into control group, heart failure group, and atorvastatin group.Either atorvastatin （10 mg· kg^-1·d^-1） or vehicle was orally administered to the rats on the next day after the surgery .The left ventricular function and NCX expression were analyzed 8 weeks after ligation .Neonatal rat cardiomyocytes were cultured to investigate the effect of atorvastatin on the changes of calcium concentration induced by hypoxemia .RESULTS： A decrease in left ventricular diastolic dimension , an increase in left ventricular fractional shortening , and reductions of BNP level and NCX expression were observed in atorvastatin group . The hypoxemiainduced calcium overload in cultured cardiomyocytes was inhibited by atorvastatin , and it was inhibited by the inhibitor of NCX .CONCLUSION：Atorvastatin treatment improves cardiac function , which may be related to the expression and function of sodium calcium exchanger in heart failure .