血管紧张素转化酶抑制剂对心衰大鼠心肌收缩特性及钙调控蛋白表达的影响

Effects of ACE inhibitor on the contractility and calcium handling proteins in ventricular myocytes from rats with heart failure

目的观察血管紧张素转化酶抑制剂(ACEI)对心衰大鼠心肌收缩特性的影响,探讨与心肌细胞钙调控蛋白NCX1、SERCA2、PLB表达水平的关系。方法缩窄Wistar大鼠腹主动脉制作心衰模型,随机分成培哚普利治疗组(CHF-T,n=16)、心衰对照组(CHF-C,n=16)和假手术组(PS,n=10)。12周后,进行心肌收缩功能测定和心肌钙调控蛋白的免疫荧光半定量分析。结果CHF-C组的左室舒张未期压力(LVEDP)高于PS组、+dp/dt和-dp/dt则较PS组为低(P均<0.05),ACE抑制剂治疗的CHF-T组则明显减轻上述改变(P均<0.05);在1.0 Hz电刺激下,CHF- T组心肌细胞缩短分数FS(%)与CHF-C组比较,有明显改善(10.89±1.18、7.51±1.15,P<0.01)。NCX1、SERCA2的蛋白表达量在CHF-T、CHF-C和PS3组间差异有统计学意义(NCX1:2988.79±149.37、3289.03±153.63、2780.61±136.57(P<0.01);SERCA2:4380.82±237.15、4092.05±185.76、4703.81±250.35,P<0.01),其中CHF-C组与PS组比较,NCX1表达明显增高、SERCA2明显降低(P<0.01);CHF-T组与CHF-C组比较,其NCX1表达显著降低(P<0.01)、SERCA2有所增高(P<0.05),但均未恢复至假手术组水平(P<0.05)。而PLB在各组间的表达差异无统计学意义(P>0.05)。结论ACEI的长程干预可以减缓心力衰竭时心肌钙调控蛋白的变化,保护心肌的收缩特性。

Objective To investigate the effects of ACE inhibitor on the contractility and calcium handling proteins in ventricular myocytes from rats with heart failure. Methods Rat heart failure models were induced by constricting abdominal aorta and randomly divided into heart failure group treated with perindopril （ CHF-T, n = 16 ）, placebo （ CHF-C, n = 16 ） and pseudo-operated groups （ PS, n = 10）. After follow-up for 12 weeks, the contractility of cardiac muscle was evaluated and the expression levels of calci- um handling proteins includeing NCX1 ,SERCA2 and PLB were measured by immumofluorescence assay. Results The value of LVEDP in group CHF-C was significantly increased as compared with that in group PS （P 〈 0.05）, and that of ± dp/dt in group CHF-C was decreased obviously as compared with that in group PS （P 〈 0.05 respectively）. In group CHF-T treated with ACEI, the deterioration above-mentioned were lessened （ P 〈 0.05）. Under the stimulation of frequencies of 1.0 Hz, the shortening fractions （FS） in group CHF-T was higher than that in group CHF-C （ 10.89 ± 1.18 vs 7.51 ± 1.15 ,P 〈 0.01 ）. There was significant difference in the expression of NCX1 and SERCA2 among CHF-T,CHF-C and PS groups （ NCX1 ： 2988.79 ± 149.37,3289.03 ± 153.63,2780.61 ± 136.57, P 〈 0.01 ; SERCA2 ： 4380.82 ± 237.15,4092.05 ± 185.76,4703.81 ± 250.35, P 〈 0.01 ）. The expression of NCX1 was higher while SERCA2 was lower in CHF-C group than in PS group （ P 〈 0.01 ）. After treatment with ACEI, the expression of NCX1 in CHF-T group was reduced significantly and the expression of SERCA2 improved obviously as compared with those in CHF-C group （ P 〈 0.01,0.05 respectively ）, but neither the expression of NCX1 or SERCA2 in CHF-T group could revert to a level just like that in PS group （ P 〈 0.05 respectively）. There was no significant difference in PLB mRNA between CHF-T and CHF-C groups. Conclusion Long-term treating CHF with ACEI can prevent the deterious changes of calcium handling proteins in CHF,which are responsible for preserving the contractility of myocytes.