DhHP‑6 attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of apoptosis

Ji,Yingshi; Yan,Xin; Hu,Yang; Xue,Huan; Sun,Jianfeng; Chen,Huaqiu; Zhang,Jiayu; Wang,Liping; Xue,Baigong; Sun,Li

doi:10.3892/mmr.2017.7569

DhHP‑6 attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of apoptosis

Authors:
- Yingshi Ji
- Xin Yan
- Yang Hu
- Huan Xue
- Jianfeng Sun
- Huaqiu Chen
- Jiayu Zhang
- Liping Wang
- Baigong Xue
- Li Sun
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Affiliations: Department of Pharmacology, Physiology and Cell Biology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Biological Chemistry, College of Life Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: September 21, 2017 https://doi.org/10.3892/mmr.2017.7569
Pages: 7229-7236
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As a novel reactive oxygen species (ROS) scavenger, deuterohemin His peptide‑6 (DhHP‑6) has been demonstrated to prolong the lifespan of Caenorhabditis elegans and has also exhibited protective effects in myocardial ischemia‑reperfusion injury. Whether similar effects occur during cerebral ischemia‑reperfusion (CIR) injury remains to be elucidated. The present study evaluated the function of DhHP‑6 and its underlying mechanisms in a middle cerebral artery occlusion (MCAO) model in rats. The focal transient MCAO model was implemented using the Longa method of ischemia for 2 h followed by reperfusion for 22 h in male Wistar rats. DhHP‑6 was administered at the onset of reperfusion via intraperitoneal injection. The infarct volume, brain edema, brain apoptosis and neurological function were evaluated 24 h following stroke. To further determine the role of DhHP‑6 in CIR injury, the levels of ROS and malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‑Px), and the protein expression levels of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax), cleaved caspase‑3, cytochrome c, Bcl‑2 and phosphorylated‑Akt/Akt were measured in ischemic cortex tissues. The results demonstrated that DhHP‑6 significantly improved infarct volume, brain edema and neurological deficits, and reduced the percentage of TUNEL‑positive cells. The levels of ROS and MDA were decreased, whereas no significant changes in the activities of SOD, CAT and GSH‑Px were observed. The levels of Bax, cleaved caspase‑3, and cytochrome c were downregulated, whereas the levels of Bcl‑2 and p‑Akt/Akt were upregulated. The results of the present study indicated that DhHP‑6 may offer therapeutic potential for cerebral ischemia. The neuroprotective effects of DhHP‑6 maybe mediated by its anti‑oxidative properties, anti‑apoptotic activities, or activation of the phosphoinositide 3‑kinase/Akt survival pathway.

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