辛伐他汀对心力衰竭家兔左室收缩功能及交感活性的影响

Simvastatin prevents decreased left ventricular systolic dysfunction in non-ischemic heart failure in rabbits via inhibition of sympathetic activity

目的:观察辛伐他汀对心力衰竭(心衰)家兔左室收缩功能和交感活性的影响,以阐明辛伐他汀改善非缺血性心衰心功能的可能机制。方法:30只家兔随机分为3组:假手术组(10只)、心衰组(10只)、辛伐他汀干预组(10mg.kg-1.d-1,10只);心衰组和辛伐他汀干预组家兔应用超容量负荷联合压力负荷建立非缺血性心衰模型,共观察7周。利用左心导管术和心脏多谱勒观察家兔血流动力学和心脏功能的变化,采用酶联免疫吸附法测定血浆脑钠肽(BNP)、去甲肾上腺素(NE)水平,以及蛋白免疫印迹法检测心肌组织蛋白激酶A(PKA)、受磷蛋白(PLB)及第16位丝氨酸磷酸化受磷蛋白(Pser16-PLB)的蛋白表达水平。结果:①与心衰组比较,辛伐他汀干预组家兔左室舒张末压、心率、血浆BNP和NE水平明显降低(P<0.05),而左室射血分数(EF)明显增加(P<0.05);②辛伐他汀干预组家兔心肌组织PKA和Pser16-PLB表达水平较心衰组家兔明显降低(P<0.05),2组间总PLB表达无明显差别。结论:辛伐他汀具有抗交感作用,是其延缓非缺血性心衰左室收缩功能减退的可能机制之一。

Objective：To invesitigate that simvastatin would prevent the decreased left ventricular systolic dysfunction in non-ischemic heart failure（HF） in rabbits via inhibition of sympathetic activity. Method：Non-ischemic HF was induced by combined aortic valve insufficiency and aortic constriction for 7 weeks.Rabbits were assigned to HF groups treated without（n=10） or with simvastatin（10 mg·kg-1·d-1,n=10） and control group with sham operation（n=10）.Cardiac function was measured using echocardiography and catheterization.Plasma norepinephrine（NE） and brain natriuretic peptide（BNP） levels were determined using ELISA assay.Protein kinase A（PKA）,total phospholamban（T-PLB） and ser16-phosphorated PLB（Pser16-PLB） abundance were determined by Western blot analysis. Result：HF rabbits with simvastatin exhibited an increased ejection fraction（P0.05）,in addition to a decreased LV end-diastolic pressure（P0.05）,heart rate and plasma levels of NE and BNP（P0.05）,compared to HF animals without treatment.Moreover,the expression of PKA（P0.05）and the ratio of Pser16-PLB to T-PLB（P0.05） were less in HF rabbits with simvastatin compared to untreated animals with HF. Conclusion：In this study,simvastatin prevents decreased left ventricular systolic dysfunction in non-ischemic heart failure in rabbits,which might be related to the inhibition of sympathetic activity.