Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3β/Nrf2 Pathway in Mice.

Rong Chen,Yan Leng,Zhong-Yuan Xia,Ling-Hua Tang,Tao Sun,Jia-Bao Hou,Yun-Yan Zhang,Zi Zeng,Qian Sun,Hui-Min Liu,Wei Li,Qing-Tao Meng,Jia-Nan Lan,Yang Wu

doi:10.1155/2020/6954764

Abstract

Aims Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. Methods C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu's score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3β/Nrf2 pathway. Results IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3β/Nrf2 pathway. Conclusion Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3β, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.β/Nrf2 pathway.

Highlights

Ischemia-reperfusion (IR) injury is a phenomenon in which the reperfusion of ischemic organs or tissues aggravates their damage [1]
We demonstrated that Ischemic postconditioning (IPO)-induced autophagy had a crucial protective role against IIR injury
IPO-induced autophagy was associated with activated Akt, inhibited GSK-3β, induced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and upregulated heme oxygenase 1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1) expression

Summary

Introduction

Ischemia-reperfusion (IR) injury is a phenomenon in which the reperfusion of ischemic organs or tissues aggravates their damage [1]. As one of the most sensitive organs to IR injury, IIR can be a life-threatening pathological event that causes local tissue injury but often leads to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). The excessive generation of reactive oxygen species (ROS) in damaged tissues and cells during IIR injury activates a variety of signaling pathways, promotes the inflammatory reaction, and damages the function of the intestinal mucosal barrier. Ischemic postconditioning (IPO) is defined as repetitive brief periods of ischemia followed by short intervals of reperfusion before the final restoration of blood flow [5]. IPO has been shown to have a strong protective effect against IR injury in the heart, brain, liver, kidney, and spi-

Methods

Results

Conclusion