Enhanced autophagy alleviates injury during hindlimb ischemia/reperfusion in mice

Liu,Chenshu; Peng,Meixiu; Zheng,Liang; Zhao,Yang; Wang,Rui; Su,Qiao; Chen,Sifan; Li,Zilun

doi:10.3892/etm.2019.7743

Enhanced autophagy alleviates injury during hindlimb ischemia/reperfusion in mice

Authors:
- Chenshu Liu
- Meixiu Peng
- Liang Zheng
- Yang Zhao
- Rui Wang
- Qiao Su
- Sifan Chen
- Zilun Li
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Affiliations: Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Division of Interventional Radiology and Vascular Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Animal Center, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Medical Research Center, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
Published online on: July 8, 2019 https://doi.org/10.3892/etm.2019.7743
Pages: 1669-1676
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies examining whether autophagy has a protective or deleterious role during ischemia/reperfusion (I/R) injury have reported a varying role in different organs and remains a matter of debate. The aim of the current study was to explore the role of autophagy in hindlimb I/R injury in a murine model. An increase in apoptosis was observed in vitro, in C2C12 myoblast cells, following hypoxia/reoxygenation (H/R), while downregulation of autophagic flux was induced by chloroquine as compared with the vehicle group under hypoxia and H/R conditions. In vivo, an increase in severe damage of gastrocnemius muscles was observed in the I/R and ischemia groups compared with the control group, was more severe in the I/R group compared with the ischemia group. Electron microscopy revealed an increased number of autophagosomes in the ischemia group, whereas a reduced number was detected in the I/R group. Following administration of rapamycin, the infarct size ratio and cell apoptosis was significantly reduced, while the amount of autophagosomes significantly increased in the ischemic phase. In conclusion, autophagy is upregulated in the ischemia phase and downregulated in the reperfusion phase. Notably, upregulation of autophagy via rapamycin intervention during ischemia alleviated skeletal muscle damage, suggesting a potential protective role during hindlimb I/R injury.

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