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

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 cardiac function in heart failure rabbits probably via downregulating myocardial CaMK Ⅱ expression and activity.