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

Biocell

article

XINGXING ZHU¹  TIANFENG HUA¹  MINGFEI WU³  JIATIAN WU¹  JIANCHAO HONG¹  MIN YANG¹ 

[1] The Second Affiliated Hospital of Anhui Medical University;The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University;School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University

关键词: Ivabradine;    Myocardial ischemia reperfusion injury;    Energy metabolism;    Oxidative stress;    AMPK/SIRT1/PGC-1α pathway;   

DOI  :  10.32604/biocell.2020.010323

学科分类：仪器

来源: Biocell

【 摘 要 】

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.

【 授权许可】

CC BY