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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 observe the effect of bisoprolol on cardiac sarcoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) activity in rats with heart failure. Methods Adriamycin intraperitoneal injection was used to establish the model of heart failure in rats. The models were randomly divided into sham-operation group, model group and bisoprolol group. Rats were fed with distilled water or bisoprolol for 35 days respectively. Cardiac function was detected by echocardiography, serum brain natriuretic peptide was detected by enzyme-linked immunosorbent assay (ELISA), miR-25-3p expression was detected by real-time polymerase chain reaction and SERCA2a and phospholamban Expression level, determination of myocardial SERCA2a activity by fixed phosphorus method. Results Compared with the sham-operation group, the cardiac output, the shortening of left ventricular (LV), the left ventricular ejection fraction (LVEF), SERCA2a and phospholamban in the model group, the ratio of SERCA2a to phosphoprotein The SERCA2a activity decreased (0.029 ± 0.025 vs 0.088 ± 0.062 U / mg pro; P <0.01), and the levels of plasma brain natriuretic peptide and myocardial miR-25-3p increased. Compared with the model group, cardiac output, FS, LVEF, SERCA2a and phospholamban level, SERCA2a and phospholamban ratio and SERCA2a activity increased significantly in bisoprolol group [SERCA2a activity (0.072 ± 0.063) vs ± 0.025) U / mg pro; P <0.05]. The levels of plasma brain natriuretic peptide and myocardial miR-25-3p were decreased. Conclusion Bisoprolol can improve cardiac function, down-regulate the expression of miR-25-3p in myocardium, increase the ratio of SERCA2a to phospholamban, and enhance the activity of SERCA2a.