基础医学与临床 ›› 2017, Vol. 37 ›› Issue (3): 386-390.

• 研究论文 • 上一篇    下一篇

比索洛尔提高心力衰竭大鼠心肌SERCA2a活性

吴锦波1,叶小汉1,冼绍祥2,董明国1   

  1. 1. 东莞市中医院
    2. 广州中医药大学第一附属医院
  • 收稿日期:2016-07-29 修回日期:2016-11-05 出版日期:2017-03-05 发布日期:2017-02-23
  • 通讯作者: 吴锦波 E-mail:wujinbocn@163.com

Bisoprolol increases myocardial SERCA2a activity in rats with heart failure

  • Received:2016-07-29 Revised:2016-11-05 Online:2017-03-05 Published:2017-02-23

摘要: 目的 观察比索洛尔对心力衰竭大鼠心肌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检测心肌肌浆网钙ATP酶(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。

关键词: 比索洛尔, 心力衰竭,充血性, 肌浆网钙ATP酶, 受磷蛋白, 微小RNA

Abstract: Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart failure.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 expression of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban(PLB) were detected by western blot analysis, 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 SERCA2a and PLB,SERCA2a activity were significantly lower than those of control 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 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<0.05). Conclusions 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.

Key words: bisoprolol, heart failure, congestive, sarcoplasmic reticulum calcium ATPase, phospholamban, microRNA