氧化应激增加可能导致门脉高压大鼠胃黏膜适应性细胞保护受损。

Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rat.

机构信息

Department of Surgery I, Oita University Faculty of Medicine, Yufu, Oita, Japan.

出版信息

J Gastroenterol Hepatol. 2013 Apr;28(4):639-44. doi: 10.1111/jgh.12101.

DOI:10.1111/jgh.12101

PMID:23278350

Abstract

BACKGROUND AND AIMS

In the gastric mucosa of portal hypertensive rats, adaptive cytoprotection against ethanol-induced damage is impaired. The aim of this study was to determine relation between impaired adaptive cytoprotection and oxidative stress.

METHODS

Portal hypertension was produced in male Sprague-Dawley rats by inducing staged portal vein occlusion. Oxidative stress levels were evaluated by measuring malondialdehyde and nitrotyrosine levels in the rat gastric mucosa with or without 10% ethanol pretreatment. Inhibition of oxidative stress by an anti-oxidant agent was estimated, and glutathione levels were also measured. Adaptive cytoprotection to 70% ethanol treatment was evaluated by measuring the gastric mucosal injury index in the presence or absence of the anti-oxidant.

RESULTS

The portal hypertensive gastric mucosa pretreated with 10% ethanol had significantly higher oxidative stress levels than the mucosa not pretreated with 10% ethanol. However, the sham-operated gastric mucosa pretreated with 10% ethanol had significantly lower oxidative stress levels than the mucosa not pretreated with 10% ethanol. Pretreatment with 10% ethanol increased glutathione levels in the sham-operated but not in the portal hypertensive gastric mucosa. Administration of the anti-oxidant agent prior to 10% ethanol pretreatment significantly reduced oxidative stress levels, increased glutathione levels, and decreased the injury index in response to 70% ethanol in the portal hypertensive gastric mucosa.

CONCLUSION

Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rats, probably through damage to the system of endogenous anti-oxidant production.

摘要

背景与目的

在门脉高压大鼠的胃黏膜中，乙醇诱导损伤的适应性细胞保护作用受损。本研究旨在确定适应性细胞保护作用受损与氧化应激之间的关系。

方法

通过诱导分期门静脉结扎术在雄性 Sprague-Dawley 大鼠中产生门脉高压。通过测量大鼠胃黏膜中丙二醛和硝基酪氨酸水平来评估氧化应激水平，这些胃黏膜在或不在 10%乙醇预处理的情况下。通过测量抗氧化剂对氧化应激的抑制作用，并测量谷胱甘肽水平来估计抗氧化应激。通过测量存在或不存在抗氧化剂时 70%乙醇处理的胃黏膜损伤指数来评估适应性细胞保护作用。

结果

用 10%乙醇预处理的门脉高压胃黏膜的氧化应激水平明显高于未经 10%乙醇预处理的胃黏膜。然而，用 10%乙醇预处理的假手术胃黏膜的氧化应激水平明显低于未经 10%乙醇预处理的胃黏膜。10%乙醇预处理增加了 sham 操作但不增加门脉高压胃黏膜中的谷胱甘肽水平。在 10%乙醇预处理前给予抗氧化剂可显著降低氧化应激水平、增加谷胱甘肽水平，并降低门脉高压胃黏膜对 70%乙醇的损伤指数。