辛伐他汀对心力衰竭家兔肌浆网钙泵的影响

Effects of Simvastatin on Sarcoplasmic Reticulum Calcium Adenosine Triphosphatase in Rabbits with Heart Failure

目的探讨家兔慢性心力衰竭时心肌肌浆网钙泵(SERCA2)表达和功能的改变及辛伐他汀长期干预的意义。方法21只家兔随机分为3组:假手术组(n=7)、心力衰竭组(n=7)和辛伐他汀组[n=7,10mg/(kg.d),主动脉关闭不全后第2天给药],通过超容量负荷联合压力负荷建立家兔心力衰竭模型,术后7周用心脏超声测定左室短轴缩短率(LVFS)及左室射血分数(LVEF),心导管术测定左室收缩末压(LVESP)、左室舒张末压(LVEDP),称量左室质量,计算左室质量指数(LVMI);用半定量RT-PCR及免疫印迹法检测SERCA2的表达,检测SERCA2活性及肌浆网摄钙能力。结果与假手术组比较,心力衰竭组家兔LVMI[(3.61±0.09)比(1.32±0.06)g/kg]、LVEDP明显升高,LVFS及LVEF[(38.5±5.1)%比(71.9±4.6)%]明显降低(均P<0.05);辛伐他汀显著降低心力衰竭家兔的LVMI[(2.17±0.13)g/kg]、LVEDP,明显升高LVFS、LVEF[(62.2±3.3)%,均P<0.05]。心力衰竭组SERCA2的表达和活性显著低于假手术组[mRNA(0.70±0.04)比(1.06±0.16),蛋白(0.69±0.04)比(1.02±0.02),活性(8.32±0.15)比(15.01±1.00)μmolPi/(mgpro.h),均P<0.05];辛伐他汀显著提高心力衰竭家兔SERCA2的表达和活性[mRNA,辛伐他汀组(0.86±0.02)比心力衰竭组(0.70±0.04);蛋白,辛伐他汀组(0.87±0.03)比心力衰竭组(0.69±0.04);活性,辛伐他汀组(11.81±0.63)比心力衰竭组(8.32±0.15)μmolPi/(mgpro.h),均P<0.05]。心力衰竭组肌浆网摄钙能力较假手术组明显降低,辛伐他汀提高心力衰竭家兔的肌浆网摄钙能力。结论辛伐他汀长期干预心力衰竭能够改善心脏舒缩功能,可能与其增加SERCA2的表达和功能有关。

Objective To investigate the expression and function of sarcoplasmic reticulum calcium adenosine triphosphatase（SERCA2） 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：sham operated group （n=7）,heart failure group （n=7） and simvastatin group [n=7,10 mg/（kg· d）].Heart failure was induced by combination of volume and pressure overload.Seven weeks later,left ventricular shorten fraction （LVFS）,left ventricular ejection fraction （LVEF）,left ventricle end-systolic pressure （LVESP）,left ventricle end-diastolic pressure （LVEDP） and left ventricular mass index （LVMI） were determined.Expression and function of SERCA2 were detected.Results Compared with the sham operated rabbits,LVMI [（3.61±0.09） vs （1.32±0.06）g/kg] and LVEDP were significantly increased LVFS,LVEF [（38.5±5.1）% vs （71.9±4.6）%] were decreased in heart failure rabbits （all P〈0.05）.Simvastatin significantly decreased LVMI [（2.17±0.13）g/kg] and LVEDP,increased LVFS and LVEF [（62.2±3.3）%] （all P〈0.05）,which was associated with increases in expression and function of SERCA2 [mRNA,heart failure group （0.70±0.04） vs sham operated group （1.06±0.16） vs simvastatin treated group （0.86±0.02）,protein：heart failure group （0.69±0.04） vs sham operated group （1.02±0.02） vs simvastatin treated group （0.87±0.03）,activity：heart failure group （8.32±0.15） vs sham operated group （15.01±1.00） vs simvastatin treated group （11.81±0.63） μmol Pi/（mg pro·h）,all P〈0.05].Conclusion Simvastatin improved cardiac function,which was associated with upregulating expression and function of SERCA2.