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