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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Authors: | XINGXING ZHU TIANFENG HUA MINGFEI WU JIATIAN WU JIANCHAO HONG MIN YANG |
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Affiliation: | 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 |
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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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Keywords: | Ivabradine Myocardial ischemia reperfusion injury Energy metabolism Oxidative stress AMPK/SIRT1/PGC-1α pathway |
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