比索洛尔对心力衰竭大鼠心肌肌浆网钙三磷酸腺苷酶2a活性的影响

The effect of bisoprolol on myocardial sarcoplasmic reticulum calcium adenosine triphosphatase 2a 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三磷酸腺苷酶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,随机分为假手术组、模型组和比索洛尔组,分别以蒸馏水或比索洛尔连续灌胃35d。心脏超声检测大鼠心功能指标,酶联免疫吸附试验(ELISA)检测血浆脑钠尿肽水平,实时定量聚合酶链反应检测心肌miR-25-3p表达水平,Western blot检测心肌SERCA2a和受磷蛋白表达水平,定磷法测定心肌SERCA2a活性。结果与假手术组比较,模型组大鼠心输出量、左心室短轴缩短率(FS)、左心室射血分数(LVEF)、心肌SERCA2a和受磷蛋白表达水平、SERCA2a与受磷蛋白比值和SERCA2a活性降低[SERCA2a活性(0.029±0.025)比(0.088±0.062)U/mg pro;P<0.01],血浆脑钠尿肽和心肌miR-25-3p表达水平升高。与模型组比较,比索洛尔组大鼠心输出量、FS、LVEF、心肌SERCA2a和受磷蛋白表达水平、SERCA2a与受磷蛋白比值和SERCA2a活性升高[SERCA2a活性(0.072±0.063)比(0.029±0.025)U/mg pro;P<0.05],血浆脑钠尿肽和心肌miR-25-3p表达水平降低。结论比索洛尔可以改善心力衰竭大鼠心功能,下调心肌miR-25-3p表达水平,提高SERCA2a与受磷蛋白比值,增强SERCA2a活性。

Objective To investigate the effect of bisoprolol on myocardial sarcoplasmic reticulum calcium adenosine triphosphatase 2a （SERCA2a） activity in rats with heart failure. Methods The rat model with heart failure was established by intraperitoneal injection of doxorubicin. Male Sprague Dawley （SD） rats were randomly divided into sham operation group （sham group）, model group, and bisoprolol group, and distilled water or bisoprolol were ad- ministered to these three groups of rats by gastrogavage for 35 days, respectively. Indices of cardiac function were measured by cardiac ultrasonography. Plasma level of brain natriuretic peptide （BNP） was determined by enzyme-linked immunosorbent assay （ELISA}. Myocardial level of miR-25-3p was detected by real-time quantitative polymerase chain reaction （PCR）. Myocardial levels of SERCA2a and phospholamban （PLN） were detected by West- ern blot, and myocardial SERCA2a activity was determined by inorganic phosphate assay. Results Compared with the sham group, cardiac output （CO）, left ventricular fractional shortening （FS）, left ventricular ejection fraction （LVEF}, myocardial levels of SERCA2a and PLN, the SERCA2a/PLN ratio, and SERCA2a activity in the model group were significantly decreased[SERCA2a activity （ 0. 029 ± 0. 025 ） vs （ 0. 088 ± 0. 062 ） U/mg pro ; P〈 0.01 ], while plasma level of BNP and myocardial level of miR-25-3p were significantly increased. Compared with the model group, CO, FS, LVEF, myocardial levels of SERCA2a and PLN, the SERCA2a/PLN ratio, and SERCA2a activity in the bisoprolol group were significantly increased[SERCA2a activity （ 0. 072 ± 0.063 ） vs （0. 029 ± 0.025） U/rag pro;P〈0.05], while plasma level of BNP and myocardial level of miR-25-3p were significantly decreased. Conclusion Bisoprolol could improve cardiac function, down-regulate the expression level of myocardial miR-25-3p, increase the SERCA2a/PLN ratio, and enhance SERCA2a activity in rats with heart failure.