MitoQ 通过调节 Nrf2 信号调节脂多糖诱导的肠道屏障功能障碍。

MitoQ Modulates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction via Regulating Nrf2 Signaling.

机构信息

Department of Intensive Care Medicine, The People's Hospital of Guangxi Zhuang Autonomous Region, China.

School of Preclinical Medicine, Guangxi Medical University, China.

出版信息

Mediators Inflamm. 2020 Apr 11;2020:3276148. doi: 10.1155/2020/3276148. eCollection 2020.

DOI:10.1155/2020/3276148

PMID:32351320

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7171662/

Abstract

BACKGROUND

Gut barrier dysfunction with alterant mucosal permeability during sepsis is a challenge problem in clinical practice. Intestinal epithelial cells (IECs) are strongly involved in mucosal oxidative stress and inflammatory response. The current study aimed at investigating the effect of MitoQ, a mitochondrial targeted antioxidant, in the treatment of intestinal injury and its potential mechanism during sepsis.

METHODS

30 minutes before sepsis induction by lipopolysaccharide (LPS) treatment, mice were treated with MitoQ. Intestinal histopathology, mucosal permeability, inflammatory cytokines, and mucosal barrier proteins were evaluated in the present study.

RESULTS

MitoQ pretreatment significantly decreased the levels of plasma diamine oxidase, D-lactate, and intestinal histological damage and markedly restored the levels of tight junction proteins (ZO-1 and occludin) following LPS challenge. Furthermore, MitoQ inhibited the LPS-induced intestinal oxidative stress and inflammatory response, evidenced by increased levels of intestinal superoxide dismutase and glutathione, and decreased levels of intestinal IL-1, IL-6, TNF-, and nitric oxide levels. Mechanically, we found that MitoQ inhibited the oxidative stress via activating nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream antioxidant genes, including HO-1, NQO-1, and GCLM.

CONCLUSIONS

MitoQ exerts antioxidative and anti-inflammatory effects against sepsis-associated gut barrier injury by promoting Nrf2 signaling pathway.

摘要

背景

脓毒症时肠道屏障功能障碍伴黏膜通透性改变是临床实践中的一个难题。肠上皮细胞（IECs）强烈参与黏膜氧化应激和炎症反应。本研究旨在探讨线粒体靶向抗氧化剂 MitoQ 在脓毒症治疗中对肠道损伤的作用及其潜在机制。

方法

在脂多糖（LPS）处理诱导脓毒症前 30 分钟，用 MitoQ 处理小鼠。本研究评估了肠道组织病理学、黏膜通透性、炎症细胞因子和黏膜屏障蛋白。

结果

MitoQ 预处理显著降低了 LPS 攻击后血浆二胺氧化酶、D-乳酸和肠道组织学损伤的水平，并显著恢复了紧密连接蛋白（ZO-1 和闭合蛋白）的水平。此外，MitoQ 抑制了 LPS 诱导的肠道氧化应激和炎症反应，表现为肠道超氧化物歧化酶和谷胱甘肽水平升高，以及肠道白细胞介素 1（IL-1）、白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和一氧化氮水平降低。机制上，我们发现 MitoQ 通过激活核因子 E2 相关因子 2（Nrf2）信号通路及其下游抗氧化基因，包括 HO-1、NQO-1 和 GCLM，抑制了氧化应激。