Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway.

The aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia-reperfusion injury via PI3K/AKT/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK-MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, apoptosis, ROS production, cytometry, activities of AKT, GSK3β, and p-38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK-MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased AKT and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β-specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation-induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia-reperfusion injury via the PI3K/AKT/ GSK3β pathway.