辛伐他汀对心力衰竭家兔蛋白激酶A及磷酸酶1α的影响

Effect of Simvastatin on Protein Kinase A and Protein Phosphatase 1 Alpha in Heart Failure Rabbit

目的:探讨家兔慢性心力衰竭(心衰)时心肌蛋白激酶 A 和磷酸酶1α蛋白表达的改变及辛伐他汀干预的意义。方法:21只家兔随机分为3组,假手术组、心衰组和辛伐他汀组各7只,通过超容量负荷联合压力负荷建立家兔心衰模型,于术后7周观察左心室结构、血流动力学的变化及心肌蛋白激酶 A、磷酸酶1α的表达。结果:血流动力学和心功能比较:与假手术组比较,心衰组左心室重量、左心室重量指数、心率、主动脉收缩压、主动脉脉压、左心室收缩末压(LVESP)、左心室舒张末压(LVEDP)、室间隔厚度、左心室后壁厚度(LVPW)、左心室舒张末径(LVDED)、左心室收缩末径(LVSED)、左心房内径显著升高,左心室缩短率及左心室射血分数显著降低,差异均有统计学意义(P 均<0.05)。与心衰组比较,辛伐他汀组的左心室重量、左心室重量指数、心率、主动脉收缩压、主动脉脉压、LVESP、LVEDP、室间隔厚度、LVPW、LVDED、LVSED、左心房内径显著降低,左心室缩短率及左心室射血分数显著升高,差异均有统计学意义(P 均<0.05)。心肌蛋白激酶 A、磷酸酶1α蛋白半定量分析结果:与假手术组比较,心衰组蛋白激酶 A 水平显著下降,而磷酸酶1α蛋白水平显著增加,差异均有统计学意义(P 均<0.05)。辛伐他汀组较心衰组蛋白激酶 A 蛋白水平显著增加,磷酸酶1α蛋白水平明显降低,差异均有统计学意义(P 均<0.05)。结论:辛伐他汀下预心衰,能够改善心脏舒缩功能,可能与其上调心肌蛋白激酶 A 表达,降低磷酸酶1α表达有关。

Objective ： To investigate the expressions of myocardial protein kinase A （PKA） and protein phosphatase 1 alpha （ PP1 α） in heart failure rabbit and the effects of simvastatin on the prevention of chronic heart failure. Methods：Twenty one rabbits were divided into three groups ：7 rabbits with heart failure induced by volume plus pressure overload （heart failure group） ,7 sham operated group, and 7 rabbits treated with simvastatin （simvastatin group）. Seven weeks later,left ventricular function, hemodynamic parameters, PKA and PP1α expression were examined. Results ：Compared with the sham operated group, heart rate （HR）, left ventricular mass index （LVMI）and left ventricular end-diastolic pressure（LVEDP） in heart failure group were significantly increased （P 〈 0. 05 ）, but their left ventricular shorten fraction and ejection fraction were decreased （ P 〈 0. 05 ）. Compared with the heart failure group, HR, LVMI and LVEDP in the simvastatin group were significantly decreased （P 〈 0. 05 ） , but their left ventricular shorten fraction and ejection fraction were increased（ P 〈0. 05 ）. PKA expression in heart failure group was remarkably lower than the sham operated group and simvastatin group respectively（ P 〈 0. 05 ）, but PP1α expression in heart failure group was remarkably higher than the sham operated group and simvastatin group respectively （ P 〈 0. 05 ）. Conclusion ： Simvastatin can improve cardiac function, probably because of its up-regulating the expression of myocardial PKA and de-regulating the expression of myocardial PP1α for preventing the heart failure.