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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 2750695, 18 pages
https://doi.org/10.1155/2018/2750695
Research Article

Polydatin Protects Diabetic Heart against Ischemia-Reperfusion Injury via Notch1/Hes1-Mediated Activation of Pten/Akt Signaling

1Department of Cardiovascular Surgery, General Hospital of Shenyang Military Region, 83 Wenhua Road, Shenyang, Liaoning 110016, China
2Department of Pharmacy, General Hospital of Shenyang Military Region, 83 Wenhua Road, Shenyang, Liaoning 110016, China
3Department of Neurosurgery, General Hospital of Shenyang Military Region, 83 Wenhua Road, Shenyang, Liaoning 110016, China
4Faculty of Life Science, Northwest University, 229 Taibai North Road, Xi’an, Shaanxi 710069, China
5Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi’an, Shaanxi 710032, China

Correspondence should be addressed to Yang Yang; moc.361@yy412002gnay and Huishan Wang; moc.621@wnahsiuh

Received 9 September 2017; Revised 21 November 2017; Accepted 6 December 2017; Published 13 February 2018

Academic Editor: Silvana Hrelia

Copyright © 2018 Liming Yu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetes exacerbates oxidative/nitrative stress during myocardial ischemia-reperfusion (MI/R) injury. Recent studies highlighted the cardioprotective actions of polydatin. However, its effect on diabetic MI/R injury and the underlying mechanisms remain unknown. This work was undertaken to evaluate the effect of polydatin on diabetic MI/R injury with a focus on Notch1/Hes1 signaling and myocardial oxidative/nitrative stress. Streptozotocin- (STZ-) induced diabetic rats were administered with polydatin (20 mg/kg/d) in the absence or presence of DAPT (a γ-secretase inhibitor) or LY294002 (a PI3K/Akt inhibitor) and then subjected to MI/R injury. Polydatin administration preserved cardiac function and reduced myocardial infarct size. Moreover, polydatin ameliorated myocardial oxidative/nitrative stress damage as evidenced by decreased myocardial superoxide generation, malondialdehyde, gp91phox expression, iNOS expression, NO metabolite level, and nitrotyrosine content and increased eNOS phosphorylation. However, these effects were blocked by DAPT administration. DAPT also inhibited the stimulatory effect of polydatin on the Notch1/Hes1-Pten/Akt signaling pathway in a diabetic myocardium. Additionally, LY294002 not only abolished polydatin’s antiapoptotic effect but also reversed its inhibitory effect on myocardial oxidative/nitrative stress. Polydatin effectively reduced MI/R injury and improved left ventricular functional recovery under diabetic condition by ameliorating oxidative/nitrative stress damage. Importantly, Notch1/Hes1-mediated activation of Pten/Akt signaling played a crucial role in this process.