缬沙坦对心力衰竭家兔肌浆网钙ATP酶、蛋白激酶A及磷酸酶1α的影响  

Effects of valsartan on sarcoplasmic reticulum calcium adenodine triphosphatase, protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart failure

作　　者：曲辅政[1] 刘志华[1] 蒋彬[1] 邹操[1] 李红霞[1] 韩莲花[1] 蒋文平[1] 

机构地区：[1]苏州大学附属第一医院心内科,215006

出　　处：《中华心血管病杂志》2008年第9期790-793,共4页Chinese Journal of Cardiology

摘　　要：目的探讨家兔慢性心力衰竭（心衰）时心肌肌浆网钙ATP酶（SERCA2）、心肌蛋白激酶A（PKA）和磷酸酶1α（PP1α）表达的改变及血管紧张素Ⅱ受体拮抗剂缬沙坦长期干预的意义。方法21只家兔随机分为三组，假手术组、心衰组和缬沙坦组各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SERCA2、PKA、PP1α的表达。结果与假手术组比较，心衰组左心室重量指数（LVMI）、心率、左心室舒张末压（LVEDP）显著升高（P〈0．05），左心室缩短率（LVFS）及射血分数（EF）明显降低（P〈0．05）；与心衰组比较，缬沙坦组LVMI、心率、LVEDP显著降低（P〈0．05），LVFS及EF明显升高（P〈0．05）；心衰组SERCA2、PKA显著低于假手术组（P〈0．05），PP1α显著高于假手术组（P〈0．05）；缬沙坦组SERCA2、PKA显著高于心衰组（P〈0．05），PP1α显著低于心衰组（P〈0．05）。结论缬沙坦长期干预心衰，能够改善心脏舒缩功能，可能与其上调SERCA2、PKA表达，降低PP1α表达有关。Objective To investigate the effects of valsartan on expressions of myocardial sarcoplasmic reticulum calcium adenodine triphosphatase （ SERCA2）, protein kinase A （PKA） and protein phosphatase 1 alpha （PP1α） in a rabbit model of heart failure. Methods Rabbits were divided into shamoperated group, heart failure group （volume overload by aortic valve destruction induced aortic insufficiency plus pressure overload induced by abdominal aortic banding） and heart failure plus valsartan （20 mg· kg^-1 · d^-1, n = 6 each）. Seven weeks later, echocardiography examination was performed and SERCA2, PKA, PP1α protein and mRNA expressions were detected by Western blot and RT-PCR. Results Compared with the with sham operated rabbits, LVMI and LVEDP in heart failure rabbits were significantly increased while left ventricular shorten fraction （LVFS） and ejection fraction （EF） were significantly decreased （all P 〈 0. 05 ）, these changes could be significantly attenuated by valsartan treatment （ all P 〈 0. 05 ）. SERCA2, PKA expressions at protein and mRNA levels were significantly downregulated and PP1α expressions significantly upregulated in heart failure rabbits than sham operated rabbits （ all P 〈 0. 05 ） and these changes could be significantly attenuated by valsartan （ all P 〈 0. 05）. Conclusion Valsartan improved cardiac function in volume and pressure overload induced heart failure rabbits possibly by upregulating expressions of myocardial SERCA2, PKA and downregulating expression of myocardial PP1α.

关 键 词：缬沙坦 心力衰竭 充血性 肌浆网 Ca(2+)转运ATP酶 环AMP依赖性蛋白激酶类 磷酸单酯水解酶类 

分 类 号：R686[医药卫生—骨科学]