Ghrelin protects the heart against ischemia/reperfusion injury via inhibition of TLR4/NLRP3 inflammasome pathway

• DOI: 10.1016/j.lfs.2017.08.004
• Publication Date: 2017-08-04T15:31:29Z
• Authors: Qin Wang; Ping Lin; Peng Li; Li Feng; Qian Ren; Xiaofeng Xie; Jing Xu
• Keywords: Male; 0301 basic medicine; Inflammasomes; Primary Cell Culture; Myocardial Reperfusion Injury; Ghrelin; Rats, Sprague-Dawley; Toll-Like Receptor 4; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Myocytes, Cardiac; Injections, Intraperitoneal; Signal Transduction

The aim of this study was to investigate the cardioprotective effects of ghrelin against myocardial ischemia/reperfusion (I/R) injury and the underlying mechanism.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.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.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.