Research Paper|Volume 12, Issue 24|pp 25120—25137

Apelin protects against ischemia-reperfusion injury in diabetic myocardium via inhibiting apoptosis and oxidative stress through PI3K and p38-MAPK signaling pathways

Songtao An¹, Xi Wang¹, Huairui, Shi², Xueqiang Zhang³, Hua Meng¹, Wenbo Li¹, Dongchang Chen¹, Junbo Ge²

¹Department of Cardiology, Henan Province People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan, China
²Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
³Department of Cardiology, Hongxing Hospital, Hami 839000, Xinjiang, China

Received: May 11, 2020Accepted: August 19, 2020Published: December 20, 2020

Copyright: © 2020 An et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Among all diabetes mellitus-associated cardiovascular diseases, morbidity of diabetic myocardium with ischemia reperfusion injury (D-IRI) is increasing year by year. We aimed to discover a therapeutic biomarker and investigate its mechanism in D-IRI. High-fat diet and streptozotocin-induced diabetes rats were operated with IRI or sham. Recombined lentiviral vector encoding Apelin was injected into D-IRI rat via tail vein. Cardiac function, infarct size, cellular death and oxidative stress were major outcome measures. Cardiomyocyte ischemia reperfusion injury was more serious in D-IRI rats than in non-diabetes ischemia reperfusion injury (ND-IRI) rats. The secretion of NTproBNP was increased in D-IRI compared with ND-IRI. Bcl-2 expression was decreased, and Bax and cleaved caspase-3 expression was increased in D-IRI rats compared with ND-IRI rats, which were reversed after treatment with Apelin. Apelin-upregulation improved cardiomyocyte ischemia reperfusion injury and decreased NT-proBNP levels in D-IRI rats. Apelin overexpression enhanced PI3K and eNOS levels while reduced those of p38-MAPK and iNOS in D-IRI rats. Apelin overexpression protected against D-IRI through inhibiting apoptosis and oxidative stress via PI3K and p38MAPK signaling pathways in D-IRI rats. These findings provide critical new insight into understanding of Apelin's cardio-protective effects, which may become a novel therapeutic target for the diabetic IRI patients.