Research Article
N-Acetylcysteine Restores Sevoflurane Postconditioning
Cardioprotection against Myocardial Ischemia-Reperfusion
Injury in Diabetic Rats
Jiefu Lin,
1
Tingting Wang,
2,3
Yalan Li,
1
Mengxia Wang,
1
Haobo Li,
2
Michael G. Irwin,
2
and Zhengyuan Xia
2,4
1
Department of Anesthesiology, Te First Afliated Hospital of Jinan University, Guangzhou 510642, China
2
Department of Anesthesiology, Te University of Hong Kong, Pokfulam, Hong Kong
3
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430022, China
4
Department of Anesthesiology, Afliated Hospital of Guangdong Medical College, Zhanjiang 524023, China
Correspondence should be addressed to Yalan Li; tyalan@jnu.edu.cn and Zhengyuan Xia; zyxia@hku.hk
Received 4 June 2015; Revised 30 July 2015; Accepted 26 August 2015
Academic Editor: Dake Qi
Copyright © 2016 Jiefu Lin et al. Tis 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.
Te efect of sevofurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with
increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection
in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four
weeks starting at fve weeks afer streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in
the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with
concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and
sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3
which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC
but not N-Acetylcysteine signifcantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic
rats displayed reduction of cardiac p-STAT3, adiponectin defciency, and increase of FoxO1 and CD36 expression, which may
be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC
cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.
1. Introduction
Ischemic heart disease (IHD) is the main cause of morbidity
and mortality in diabetes. Patients with diabetes are particu-
larly at risk of perioperative myocardial infarction with con-
sequent ischemia and reperfusion injury (IRI). Sevofurane
postconditioning (sevo-postC) has been shown to attenuate
myocardial IRI by restraining the adhesion of infammatory
cells, blocking up free oxygen radicals, and preventing cal-
cium overload [1]. However, the benefcial efect of sevo-
PostC is markedly attenuated by diabetes and the underlying
mechanism is unclear. Diabetes can cause impairments to
both phosphatidylinositol 3-kinase- (PI3K-) Akt and Janus
kinase (Jak-) STAT3, which are the two classic signaling
pathways of myocardial protection mechanisms and thus
obstruct the postconditioning of myocardium [2, 3]. Recent
studies indicated that the inability of insulin to restore sevo-
postC cardioprotection in diabetes might be attributed to
diabetes-induced STAT3 mediated inhibition of PI3K signal-
ing [4]. Interestingly, our previous study has demonstrated
that antioxidant N-Acetylcysteine (NAC) can partially restore
the activation of Akt and STAT3 and subsequently attenuated
myocardial IRI in the early stage of diabetic rats [5, 6].
However, whether NAC can restore the cardioprotection
of sevo-IPostC through the restoration of STAT3 mediated
signaling remains unknown.
Hindawi Publishing Corporation
Journal of Diabetes Research
Volume 2016, Article ID 9213034, 8 pages
http://dx.doi.org/10.1155/2016/9213034