比索洛尔对心力衰竭大鼠心肌肌浆网钙ATP酶2a活性的影响

Effects of bisoprolol on myocardial SERCA2a activity in rats with heart failure

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:采用阿霉素腹腔注射法建立大鼠心力衰竭模型,随机分为正常对照组、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,分别以蒸馏水、比索洛尔、卡托普利、比索洛尔+卡托普利连续灌胃35d。观察大鼠心功能指标,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PLB蛋白表达水平,定磷法测定心肌SERCA2a活性。结果: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指标明显高于模型组,血浆脑钠肽水平明显低于模型组,miR-25-3p表达水平明显低于模型组,SERCA2a和受磷蛋白(PLB)蛋白表达水平明显高于模型组(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<0.01或P<0.05),卡托普利组与模型组比较无明显差异。结论:比索洛尔可以改善心力衰竭大鼠心功能,机制可能与下调心肌miR-25-3p表达水平,提高SERCA2a、PLB表达水平,提升SERCA2a/PLB比值,增强SERCA2a活性有关。

Objective：To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart failure.Method：Male SD rats were randomly divided into normal control group（normal 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 was administrated respectively by gastrogavage for 35 days.Indices of cardiac function and plasma levels of B-type natriuretic peptide（BNP）were measured.Myocardial expression level of miR-25-3p was detected by Stem-loop RT-PCR.Myocardial protein expression levels of SERCA2a and phospholamban（PLB）were detected by western blot analysis.Myocardial SERCA2a activity was determined by the inorganic phosphorus method.Result：Indices of cardiac function in Bis group,Cap group and Bis＋Cap group were significantly higher while plasma levels of BNP were significantly lower than those of model group（P〈0.01）.Myocardial expression levels of miR-25-3p in Bis group,Cap group and Bis＋Cap group were significantly lower while myocardial protein expression levels of SERCA2a and PLB were significantly higher than those of 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〈0.01 or P〈0.05）,but no significant change was observed between Cap group and model group.Conclusion：Bisoprolol therapy improves cardiac function in rats with heart failure,which may be related to downregulation of myocardial miR-25-3p expression,upregulation of myocardial SERCA2a and PLB protein expression,increasing the SERCA2a/PLB ratio,and enhancing SERCA2a activity.