比索洛尔提高心力衰竭大鼠心肌SERCA2a活性

摘要

Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart fail-ure.Methods Male SD rats were randomly divided into normal control group (control group), sham operation group ( sham group ) , model group , bisoprolol group ( Bis group ) , captopril group ( Cap group ) and bisoprolol plus captopril group[(Bis+Cap)group], heart failure rat model was induced by intraperitoneal injections of doxorubicin .Distilled water, bisoprolol, captopril or bisoprolol plus captopril were administrated by gastrogavage for 35 days, respectively. Indices of cardiac function and plasma levels of B-type natriuretic peptide ( BNP) were measured , myocardial expres-sion of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban (PLB) were detected by Western blot , myocardial SERCA2a activity was determined by the inorganic phosphorus method . Results Cardiac function in model group decreased significantly while plasma levels of BNP were significantly higher than those of control group ( P<0.01 ) .Myocardial expression of miR-25-3p in model group was significantly higher while myocardial levels of SERCA 2a and PLB,SERCA2a activity were significantly lower than those of con-trol group(P<0.01).Cardiac function in Bis group , Cap group and Bis +Cap group improved significantly while plasma levels of BNP were significantly lower than those of model group ( P<0.01 ) .Myocardial expression of miR-25-3p in Bis group, Cap group and Bis +Cap group were significantly lower while myocardial levels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Bis group and Bis +Cap group were significantly higher than those of model group ( P<0.05 ) .Conclu-sions Bisoprolol therapy improves cardiac function in rats with heart failure , which may be related to inhibition of myocardial miR-25-3p, increasing myocardial SERCA2a and PLB levels, enhancing SERCA2a activity.%目的 观察比索洛尔对心力衰竭大鼠心肌肌浆网钙ATP酶2a(SERCA2a)活性的影响.方法 腹腔注射阿霉素建立大鼠心力衰竭模型.实验分为对照组、假手术组、模型组、比索洛尔组、卡托普利组和比索洛尔+卡托普利组.检测心功能指标;ELISA法检测血浆脑钠肽水平;茎环状引物实时定量PCR检测心肌miR-25-3p表达水平;Western blot检测心肌SERCA2a和受磷蛋白(PLB)表达水平;定磷法测定心肌SERCA2a活性.结果 与对照组比较,模型组大鼠心功能明显减退(P<0.01),血浆脑钠肽水平和心肌miR-25-3p表达水平明显升高(P<0.01),SERCA2a和PLB表达水平、SERCA2a/PLB比值和SERCA2a活性明显降低(P<0.01);与模型组比较,比索洛尔组、卡托普利组和比索洛尔+卡托普利组大鼠心功能明显改善(P<0.01),血浆脑钠肽水平和心肌miR-25-3p表达水平明显降低(P<0.01),SERCA2a和PLB表达水平明显升高(P<0.01);比索洛尔组和比索洛尔+卡托普利组SERCA2a/PLB比值和SERCA2a活性明显高于模型组(P<0.05).结论 比索洛尔可以下调心肌miR-25-3p表达水平,提高SERCA2a和PLB表达水平,增强SERCA2a活性.