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

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受体拮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CaMK Ⅱ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)、左窒舒张末压显著升高(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、左室舒张未压显著降低(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CaMK Ⅱ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CaMK Ⅱ蛋白表达及活性有关.

Effects of valsartan on myocardial calcium/calmodulin-dependent protein kinase-Ⅱ expression and activity in a rabbit model of heart failure

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 insuffiency plus pressure overload induced bv abdominal aortic banding)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 ventrieular mass indexLVMI(3.61±0.09)g/kg vs.(1.32±0.06)g/kg,P＜0.05]and end-diastolic pressureLVEDP(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 ventricular shortening fractionsLVFS(17.38±3.13)%vs.(37.83±3.58)%,P＜0.05]and ejection fractionLVEF(38.50±6.07)%vs.(71.92±4.56)%,P＜0.05]were significantly decreased(all P＜0.05)in heart failure rabbits,these changes could be significantly attenuated by vasartan 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＜0.05],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].CaMK Ⅱ expression(1.45 ±0.13 vs 0.89±0.05,1.13±0.12,P＜0.05)and operated rabbits which could be significantly attenuated by valsartan treatment.Conclusion Valsatan improved cardiac function in heart failure rabbits probably via downregulating myocardial CaMK Ⅱ expression and activity.