1. The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway
- Author
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Yu-Sheng Liu, Qing-Hua Lu, Jiannan Huang, Yi Li, and Juan Zhang
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Growth hormone secretagogue receptor ,Ischemia ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Growth hormone secretagogue ,Malondialdehyde ,Internal medicine ,Animals ,Medicine ,Myocytes, Cardiac ,Growth Substances ,Receptors, Ghrelin ,Receptor ,business.industry ,Myocardium ,Heart ,General Medicine ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Ghrelin ,Cardiology and Cardiovascular Medicine ,business ,Oligopeptides ,Reperfusion injury ,Interleukin-1 ,Signal Transduction ,Hormone - Abstract
Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 μg/kg·day], ghrelin [400 μg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1β, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist [D-Lys3]-growth hormone releasing peptide-6 ([D-Lys3]-GHRP-6). These findings suggest that hexarelin protects in vivo cardiomyocytes from I/R injury partly by modification of the IL-1 signaling pathway through the activation of cardiac GHSR1a receptors.
- Published
- 2017