家兔心力衰竭早期心肌受磷蛋白磷酸化程度增加

Phosphorylation of phospholamban at Ser16 is increased in myocardium of rabbits with mild heart failure

目的:探讨心力衰竭(心衰)心肌细胞磷酸化受磷蛋白表达异常的临床意义。方法:将20只家兔随机分为两组:假手术组和心衰组,各10只。通过超容量负荷联合压力负荷建立家兔心衰模型,利用心导管术和心脏多普勒观察手术前后家兔血流动力学及心脏结构和功能的变化。采用蛋白免疫印迹(Western blot)法测定心肌组织蛋白激酶A(PKA)、总受磷蛋白(T-PLB)和第16位丝氨酸磷酸化受磷蛋白(ser16-P-PLB)表达水平。结果:家兔心衰组与假手术组相比,左室舒张末压明显增加,为(-7±4.6)mmHg对(24.6±6.7)mmHg,左室短轴缩短率[(39.3±5.53)%对(23.8±7.30)%]和左室射血分数[(72.76±4.85)%对(47.8±6.05)%]均明显降低(P<0.01)。心肌组织T-PLB表达无明显差异,PLB磷酸化程度Ser16-P-PLB/T-PLB和PKA表达均增加。结论:心衰早期心肌受磷蛋白磷酸化程度表达增加,与蛋白激酶A表达增加有关。

Objective：To investigate the abnormal abundances of phosphlamban phosphorylation at Ser16 in eardiomyoeytes of rabbit with mild heart failure. Methods：Twenty rabbits were divided into two groups.. 10 rabbits with heart failure induced by volume plus pressure overload and 10 sham-operated animals. The hemodynamic parameters and cardiac structure and function were detected via catheterization and eehoeardiography, respectively. Protein kinase A （PKA）, phospholanban （PLB） and phosphorylation of Serl6- phospholamban （P-Ser16-PLB） protein abundances were determined by Western blot analysis. Results： Left ventrieular end diastolic pressure in heart failure rabbits was significantly increased compared with that in shamoperated rabbits（ - 7 ±4. 6 vs 24.6 ± 6. 7,P〈0. 01） ,while their left ventricular shorting fraction [-（39. 3± 5.53）% vs （23.8 ± 7.30） %] and ejection fraction [-（72.76 ± 4. 85）% vs （47.8 ± 6.05） %] were decreased （P〈0.01 ）. In heart failure rabbits, there was no significant difference with the abundances of T-PLB（RT-PLB/actin：1. 12± 0. 023 vs 1. 11 ± 0. 045, P = 0. 069）, whereas the expressions of Ser16-P-PLB, the degree of phospholamban phosphorylation at Serl6 and PKA were markedly increased. Conclusion.. In early stage of heart failure, the increased phosphorylation of phospholamban at Serl6, which is due to increased expression of PKA, may contribute to maintenance of cardiac performance.