Cardioprotective effect of ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway in myocardial ischemia/reperfusion injury induced in H9c2 cell

Post-resuscitation myocardial dysfunction (PRMD) is the most severe myocardial ischemia-reperfusion injury(MIRI) and is characterized by difficult treatment and poor prognosis. Research has shown the protective effects of therational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In thisstudy, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstratedthat pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis. IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species (ROS), suppressed IRI-induced ATP and NAD⁺, and increased theAMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 (SIRT1) and peroxisomeproliferator-activated receptor-γ coactivator 1α (PGC-1α) and upregulated the expression levels of phosphorylatedAMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPKmRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this studywas to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway inmyocardial ischemia/reperfusion injury-induced in H9c2 cell.