摘要
目的探讨家兔慢性心力衰竭（心衰）时心肌细胞核及肌浆网钙调蛋白依赖性蛋白激酶Ⅱ（CaMKII）蛋白表达和活性的改变，以及血管紧张素Ⅱ受体拮抗剂缬沙坦长期干预的意义。方法24只家兔随机分为3组，假手术组、心衰组和缬沙坦组，各8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CaMKⅡ的表达和活性的改变。结果与假手术组比较，心衰组左心室重量指数（LVMI）[（3．61±0．09）g／kg比（1．32±0．06）g／kg，P〈0．05]、左心室舒张末压（LVEDP）[（23．00±2．37）mmHg比（-1．50±0．50）mmHg，P〈0．05]显著升高，左心室缩短率（LVFS）[（17．38±3．13）％比（37．83±3．58）％，P〈0．05]及左室射血分数（LVEF）[（38．50±6．07）％比（71．92±4．56）％，P〈0．05]明显降低。与心衰组比较，缬沙坦组LVMI[（2．07±0．14）g／kg比（3．61±0．09）g／kg，P〈0．05]和LVEDP[（2．17±0．72）mmHg比（23．00±2．37）mmHg，P〈0．05]显著降低，LVFS[（33．83±2．85）％比（17．38±3．13）％，P〈0．05]和LVEF[（64．45±3．66）％比（38．50±6．07）％，P〈0．05]明显升高。心衰组细胞核及肌浆网CaMKⅡ蛋白表达（1．42±0．11比0．86±0．04，1．39±0．14比0．80±0．06，P〈0．05）及活性（3．43±0．15比2．14±0．13，3．38±0．11比2．09±0．11，P〈0．05）显著高于假手术组；缬沙坦组细胞核及肌浆网CaMKⅡ蛋白表达（1．18±0．11比1．42±0．11，1．10±0．11比1．39±0．14，P〈0．05）及活性（2．72±0．13比3．43±0．15，2．69±0．12比3．38±0．11，P〈0．05）显著低于心衰组。结论缬沙坦长期干预心力衰竭，能够改善心脏舒缩功能，可能与其降低细胞核及肌浆网CaMKⅡ蛋白表达及活性有关。
Objective To investigate the expression and activity of Calcium/calmodulin-dependent pro- tein kinase- Ⅱ（ CaMK Ⅱ ） in nucleus and sarcoplasmic reticulum in heart failure rabbit and the effects of Valsartan on the prevention of chronic heart failure. Methods 24 rabbits were divided into three groups：8 rabbits with heart failure induced by volume overload plus pressure overload, 8 sham rabbits and 8 rabbits those were treated with Valsartan. 7 weeks later, left ventricular function, hemodynamic parameters, expression and activity of CaMK Ⅱ were observed. Results Compared with the sham operated rabbits, LVMI[（3.61±0.09）g/kg vs （1.32±0.06）g/kg, P〈0.05） and LVEDP[（23.00±2.37）mm Hg vs （-1.50±0.50）mm Hg, P〈0.051 in heart failure rabbits were signif- icantly increased, but their left ventricular shorten fraction [LVFS （17.38±3.13）% vs （37.83±3.58）%, P〈0.05 ] and left ventricular ejection fraetion[LVEF （38.50±6.07）% vs （71.92±4.56）%, P〈0.05] were decreased. Com- pared with the heart failure rabbits, LVMI[（2.07±0.14）g/kg vs （3.61±0.09）g/kg, P〈0.05] and LVEDP[（2.17±0.72）mm Hg vs （23.00±2.37）mm Hg, P〈0.05 ] in the Valsartan treated rabbits were significantly decreased, but their 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] were increased. Expression （1.42±0.11 vs 0.86±0.04, 1.18±0.11, P〈0.05） （1.39±0.14 vs 0.80±0.06, 1.10±0.11, P〈0.05） and activity（3.43±0.15 vs 2.14±0.13, 2.72±0.13, P〈0.05）（3.38±0.12 vs 2.09±0.11, 2.69±0.12, P〈0.05 ） of CaMK Ⅱ in nucleus and sareoplasmic reticulum in heart failure rabbits were remarkably higher than sham operated rabbits and valsartan treated rabbits respectively. Conclusion Valsartan can improve cardiac function, probably owing to its disregulating expression and activity of CaMK Ⅱ in nucleus and sarcoplasmic reticu- lum on the prevention of heart failure.
出处
《中国心血管病研究》
CAS
2015年第8期759-763,共5页
Chinese Journal of Cardiovascular Research
