摘要
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。
Objective To investigate the effects of bisoprolol on myocardial SERCA2 a 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-q PCR,myocardial levels of SERCA2 a and phospholamban（ PLB）were detected by Western blot,myocardial SERCA2 a 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 significantlyhigher while myocardial levels of SERCA2 a and PLB,SERCA2 a 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 SERCA2 a and PLB were significantly higher than those in model group（ P 0. 01）. The SERCA2 a / PLB ratio and SERCA2 a 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 SERCA2 a and PLB levels,enhancing SERCA2 a activity.
出处
《基础医学与临床》
CSCD
2017年第3期386-390,共5页
Basic and Clinical Medicine
关键词
比索洛尔
心力衰竭
充血性
肌浆网钙ATP酶
受磷蛋白
bisoprolol
heart failure
congestive
sarcoplasmic reticulum calcium ATPase
phospholamban
