缬沙坦对心力衰竭家兔钙调蛋白依赖性蛋白激酶Ⅱ的影响  

Effects of valsartan on myocardial calcium/calmodulin-dependent protein kinase-Ⅱ expression and activity 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》2009年第6期501-504,共4页Chinese Journal of Cardiology

基　　金：基金项目：江苏省自然科学基金资助项目（BK2005034）

摘　　要：目的探讨家兔慢性心力衰竭（心衰）时心肌钙调蛋白依赖性蛋白激酶Ⅱ（CaMKⅡ）蛋白表达及活性的改变及血管紧张素Ⅱ受体拈抗剂缬沙坦长期干预的意义。方法27只家兔随机分为3组，假手术组、心衰组和缬沙坦组各9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、血液动力学的变化及CaMKⅡ的表达和活性的改变。结果与假手术组比较，心衰组左室重量指数（LVMI）、左室舒张末压显著升高（P〈0．05），左室短轴缩短率及左室射血分数明显降低（P〈0．05）；与心衰组比较，缬沙坦组左室重量指数、左室舒张末压显著降低（P〈0．05），左室短轴缩短率及左室射血分数明显升高（P〈0．05）；心衰组CaMKⅡ蛋白表达及活性显著高于假手术组（P〈0．05）；缬沙坦组CaMKⅡ蛋白表达及活性显著低于心衰组（P〈0．05）。结论缬沙坦长期干预心衰，能够改善心脏舒缩功能，可能与其降低CaMKⅡ蛋白表达及活性有关。Objective To investigate the effects of valsartan on myocardial expression and activity of calcium/calmodulin-dependent protein kinase- Ⅱ （ CaMK Ⅱ ） in a rabbit model of heart failure. Methods Rabbits were divided into sham-operated 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 = 9 each ）. Seven weeks later, eehocardiography and hemodynamic examinations were performed and myocardial CaMK Ⅱ expression and activity were detected by Western blot and CaMK Ⅱ activity assay kit, respectively. Results Compared with the sham operated rabbits,left ventricular mass index [ LVMI （3.61 ± 0. 09） g/kg vs. （ 1.32 ± 0. 06） g/kg, P 〈 0. 05 ] and end-diastolic pressure [ LVEDP （23.00 ± 2. 37） mm Hg（ 1 mm Hg = 0. 133 kPa） vs. （ - 1.50 ± 0. 5） mm Hg, P 〈 0. 05 ] were significantly increased while left ventrieular shortening fractions [ LVFS （ 17.38 ± 3.13）% vs. （37.83 ±3.58）% , P 〈0. 05] and ejection fraction [LVEF （38.50 ±6.07）% vs. （71.92 ± 4. 56） % , P 〈 0.05 3 were significantly decreased （ all P 〈 0. 05 ） in heart failure rabbits, these changes could be significantly attenuated by valsartan treatment： LVMI [ （2.07 ±0. 14 ） g/kg vs. （3.61 ± 0. 09 ） g/kg, P〈0.05], LVEDP [（2.17 ±0.72） mm Hg vs. （23.00 ±2.37） mm Hg, P〈0. 051, LVFS [（33.83 ±2. 85）% vs. （17.38±3.13）%, P〈0. 05] and LVEF [（64.45 ±3.66）% vs. （38.50± 6. 07）%, P〈0. 05].CaMKⅡ expression （1.45±0.13 vs 0.89±0.05, 1.13±0.12, P〈0.05） and activity [（3.54 ±0. 17）pmol·min^-1·μg^-1 vs. （2. 18 ±0. 13） pmol·min^-1·μg^-1, （2. 79 ±0. 14）pmol·min^-1·μg^-1, p 〈 0. 05 ] in heart failure rabbits were significantly increased than those sham operated rabbits which could be significantly attenuated by valsartan treatment. Conclusion Valsartan improved car

关 键 词：缬沙坦 心力衰竭 充血性 血液动力学 钙(2+)-钙调蛋白依赖性蛋白激酶 

分 类 号：R686[医药卫生—骨科学]