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辐射暴露后小鼠小肠黏膜抗氧化网络失衡。

Imbalance of the antioxidant network of mouse small intestinal mucosa after radiation exposure.

作者信息

Haton Céline, François Agnès, Vandamme Marie, Wysocki Julie, Griffiths Nina M, Benderitter Marc

机构信息

Département de RadioProtection de l'Homme, Laboratoire de radiopathologie, Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France.

出版信息

Radiat Res. 2007 Apr;167(4):445-53. doi: 10.1667/RR0581.1.

Abstract

The aim of this study was to investigate acute variations in antioxidant defense systems in the intestinal mucosa after abdominal radiation exposure and the role played by radiation-induced inflammation in these variations. Antioxidant defense systems of mouse small intestinal mucosa were studied at 6 h and 4 days after abdominal radiation exposure. Superoxide dismutases, glutathione peroxidases, catalase, metallothioneins and thioredoxins were followed in terms of mRNA expression, protein expression and enzyme activities. Dexamethasone was administered to investigate the relationship between variations in mucosal antioxidant capacity and radiation-induced inflammation. Six hours after exposure, only mitochondrial-associated antioxidant systems were induced (the superoxide dismutase and thioredoxin 2). Four days after exposure, during the inflammatory phase, superoxide dismutases were decreased and modulations of the second line of the antioxidant network were also observed: Catalase was decreased and glutathione peroxidases and metallothioneins were induced. Dexamethasone treatment modulated only glutathione peroxidase expression and did not influence either metallothionein or superoxide dismutase expression. Our findings provide direct in vivo evidence that antioxidant mechanisms of the small intestinal mucosa were not markedly mobilized during the very acute tissue radiation response. During the radiation-induced acute inflammatory response, the antioxidant capacity appeared to be dependent on inflammatory status to a certain extent.

摘要

本研究的目的是调查腹部辐射暴露后肠黏膜抗氧化防御系统的急性变化,以及辐射诱导的炎症在这些变化中所起的作用。在腹部辐射暴露后6小时和4天研究了小鼠小肠黏膜的抗氧化防御系统。从mRNA表达、蛋白质表达和酶活性方面对超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、金属硫蛋白和硫氧还蛋白进行了跟踪研究。给予地塞米松以研究黏膜抗氧化能力变化与辐射诱导的炎症之间的关系。暴露后6小时,仅诱导了与线粒体相关的抗氧化系统(超氧化物歧化酶和硫氧还蛋白2)。暴露后4天,在炎症阶段,超氧化物歧化酶减少,同时也观察到抗氧化网络二线的调节:过氧化氢酶减少,谷胱甘肽过氧化物酶和金属硫蛋白被诱导。地塞米松处理仅调节谷胱甘肽过氧化物酶的表达,而不影响金属硫蛋白或超氧化物歧化酶的表达。我们的研究结果提供了直接的体内证据,表明在非常急性的组织辐射反应期间,小肠黏膜的抗氧化机制并未明显调动。在辐射诱导的急性炎症反应期间,抗氧化能力在一定程度上似乎依赖于炎症状态。

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