Open Access

ARTICLE

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

XINGXING ZHU^1,2, TIANFENG HUA^1,2, MINGFEI WU³, JIATIAN WU^1,2, JIANCHAO HONG^1,2, MIN YANG^1,2,*

1 The Second Affiliated Hospital of Anhui Medical University, Hefei, China
2 The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
3 School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, China

* Address correspondence to: Min Yang,

BIOCELL 2020, 44(3), 431-441. https://doi.org/10.32604/biocell.2020.010323

Received 26 February 2020; Accepted 26 May 2020; Issue published 22 September 2020

Abstract

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 the rational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In this study, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstrated that 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 the AMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and upregulated the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPK mRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.

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