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厄多司坦和依布硒啉作为肠道缺血/再灌注损伤的有效药物。

Erdosteine and ebselen as useful agents in intestinal ischemia/reperfusion injury.

作者信息

Tunc Turan, Uysal Bulent, Atabek Cuneyt, Kesik Vural, Caliskan Bahadir, Oztas Emin, Ersoz Nail, Oter Sukru, Guven Ahmet

机构信息

Department of Pediatrics, Gulhane Military Medical Academy, Etlik, Ankara, Turkey.

出版信息

J Surg Res. 2009 Aug;155(2):210-6. doi: 10.1016/j.jss.2008.06.017. Epub 2008 Jul 15.

DOI:10.1016/j.jss.2008.06.017
PMID:19505699
Abstract

BACKGROUND

Reactive oxygen and nitrogen species generated during reperfusion of the tissue are characteristic of ischemia/reperfusion (I/R) injury. The purpose of the present study was to investigate whether erdosteine and ebselen, molecules with antioxidant properties and peroxynitrite scavenging capability, respectively, can reduce oxidative stress and histological damage in the rat small bowel subjected to mesenteric I/R injury.

MATERIALS AND METHODS

Forty Sprague-Dawley rats were divided into five groups equally: sham, I/R, I/R plus erdosteine, I/R plus ebselen, and I/R plus erdosteine and ebselen. Intestinal ischemia for 45 min and reperfusion for 3 d were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehide (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitrite/nitrate (NO(x)) level and histological changes.

RESULTS

Intestinal I/R resulted in increased tissue MDA, PCC, and NO(x) levels and decreased SOD and GPx activities. Both erdosteine and ebselen alone significantly decreased MDA, PCC, and NO(x) levels and increased antioxidant enzymes activities, but all values were different from control. These changes almost returned to control values in the group treated with erdostein and ebselen. Histopathologically, the intestinal injury in rats treated with erdosteine and ebselen as well as combination were less than I/R group.

CONCLUSIONS

Both erdosteine and ebselen were able to attenuate I/R injury of the intestine via inhibition of lipid peroxidation and protein oxidation, maintenance of antioxidant, and free radical scavenger properties. Nevertheless, combination treatment showed more promising results, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing intestinal I/R injury.

摘要

背景

组织再灌注过程中产生的活性氧和氮物质是缺血/再灌注(I/R)损伤的特征。本研究的目的是调查具有抗氧化特性和过氧亚硝酸盐清除能力的厄多司坦和依布硒仑是否能减轻肠系膜I/R损伤大鼠小肠的氧化应激和组织学损伤。

材料与方法

40只Sprague-Dawley大鼠平均分为五组:假手术组、I/R组、I/R加厄多司坦组、I/R加依布硒仑组以及I/R加厄多司坦和依布硒仑组。进行45分钟的肠缺血和3天的再灌注。获取回肠标本以测定组织丙二醛(MDA)水平、蛋白质羰基含量(PCC)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、亚硝酸盐/硝酸盐(NO(x))水平以及组织学变化。

结果

肠I/R导致组织MDA、PCC和NO(x)水平升高,SOD和GPx活性降低。单独使用厄多司坦和依布硒仑均显著降低了MDA、PCC和NO(x)水平,并提高了抗氧化酶活性,但所有数值均与对照组不同。在厄多司坦和依布硒仑联合治疗组中,这些变化几乎恢复到了对照值。组织病理学检查显示,厄多司坦和依布硒仑单独及联合治疗组大鼠的肠损伤均小于I/R组。

结论

厄多司坦和依布硒仑均能够通过抑制脂质过氧化和蛋白质氧化、维持抗氧化和自由基清除特性来减轻肠I/R损伤。然而,联合治疗显示出更有前景的结果,表明在预防肠I/R损伤中,在抗氧化活性附近清除过氧亚硝酸盐很重要。

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