缺血后处理通过激活 Akt/GSK-3/Nrf2 通路增强自噬和抑制氧化应激减轻小鼠肠缺血再灌注损伤。

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

机构信息

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

Zhongnan Hospital of Wuhan University, Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China.

出版信息

Oxid Med Cell Longev. 2020 Mar 14;2020:6954764. doi: 10.1155/2020/6954764. eCollection 2020.

DOI:10.1155/2020/6954764

PMID:32256957

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7102478/

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-3/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-3/Nrf2 pathway.

CONCLUSION

Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury./Nrf2 pathway.

摘要

目的

缺血后处理（IPO）对肠缺血再灌注（IIR）损伤具有强烈的保护作用，部分与自噬有关。然而，其具体机制尚不清楚。

方法

C57BL/6J 小鼠接受单侧 IIR 合并或不合并 IPO。缺血 45 分钟和再灌注 120 分钟后，收集肠组织和血液进行检查。HE 染色和 Chiu 评分用于评估病理损伤。我们检测了肠屏障功能和氧化应激的标志物。最后，我们使用 WB 检测自噬和 Akt/GSK-3/Nrf2 通路的关键蛋白表达。