Qin Wang1, Ping Lin2, Peng Li1, Li Feng1, Qian Ren1, Xiaofeng Xie1, Jing Xu1. 1. Department of Geriatrics, The 3rd Hospital of Hangzhou, Hangzhou, China. 2. Department of Geriatrics, The 3rd Hospital of Hangzhou, Hangzhou, China. Electronic address: linp916@yahoo.com.
Abstract
AIMS: The aim of this study was to investigate the cardioprotective effects of ghrelin against myocardial ischemia/reperfusion (I/R) injury and the underlying mechanism. MAIN METHODS: Sprague-Dawley rats were randomized into Sham, I/R and I/R+ghrelin groups. After 30 minutes ischemia, ghrelin (8nmol/kg) was injected intraperitoneally at the time of reperfusion in the I/R+ghrelin group. Then hemodynamic parameters were observed at 24h after reperfusion. KEY FINDINGS: Ghrelin exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ±dP/dtmax and decreased LVDP. At 24h after reperfusion, ghrelin significantly attenuated the myocardial infarction area and apoptosis, accompanied with a decrease in the levels of the myocyte injury marker enzymes. Oxidative stress injury and inflammatory response were also relieved by ghrelin. Western blot showed that the expression of TLR4, NLRP3, and caspase-1 were obviously increased in I/R group, while ghrelin significantly inhibited the I/R-induced TLR4, NLRP3, and caspase-1 expression. Ghrelin could inhibit the increased protein levels of NLRP3, caspase-1, and IL-1β induced by lipopolysacharide in primary cultured cardiomyocytes of neonatal rats. SIGNIFICANCE: Ghrelin protected the heart against I/R injury by inhibiting oxidative stress and inflammation via TLR4/NLRP3 signaling pathway. Our results might provide new strategy and target for treatment of myocardial ischemia/reperfusion injury.
AIMS: The aim of this study was to investigate the cardioprotective effects of ghrelin against myocardial ischemia/reperfusion (I/R) injury and the underlying mechanism. MAIN METHODS:Sprague-Dawley rats were randomized into Sham, I/R and I/R+ghrelin groups. After 30 minutes ischemia, ghrelin (8nmol/kg) was injected intraperitoneally at the time of reperfusion in the I/R+ghrelin group. Then hemodynamic parameters were observed at 24h after reperfusion. KEY FINDINGS:Ghrelin exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ±dP/dtmax and decreased LVDP. At 24h after reperfusion, ghrelin significantly attenuated the myocardial infarction area and apoptosis, accompanied with a decrease in the levels of the myocyte injury marker enzymes. Oxidative stress injury and inflammatory response were also relieved by ghrelin. Western blot showed that the expression of TLR4, NLRP3, and caspase-1 were obviously increased in I/R group, while ghrelin significantly inhibited the I/R-induced TLR4, NLRP3, and caspase-1 expression. Ghrelin could inhibit the increased protein levels of NLRP3, caspase-1, and IL-1β induced by lipopolysacharide in primary cultured cardiomyocytes of neonatal rats. SIGNIFICANCE: Ghrelin protected the heart against I/R injury by inhibiting oxidative stress and inflammation via TLR4/NLRP3 signaling pathway. Our results might provide new strategy and target for treatment of myocardial ischemia/reperfusion injury.
Authors: Beatriz Ferrer; Harshini Suresh; Alexey A Tinkov; Abel Santamaria; João Batista Rocha; Anatoly V Skalny; Aaron B Bowman; Michael Aschner Journal: Mol Neurobiol Date: 2022-01-18 Impact factor: 5.590
Authors: Ricardo O S Soares; Daniele M Losada; Maria C Jordani; Paulo Évora; Orlando Castro-E-Silva Journal: Int J Mol Sci Date: 2019-10-11 Impact factor: 5.923