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胍丁胺通过减轻大鼠氧化应激和炎症反应来减轻肠缺血再灌注损伤。

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

作者信息

Turan Inci, Ozacmak Hale Sayan, Ozacmak V Haktan, Barut Figen, Araslı Mehmet

机构信息

Department of Physiology, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey.

Department of Physiology, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey.

出版信息

Life Sci. 2017 Nov 15;189:23-28. doi: 10.1016/j.lfs.2017.08.032. Epub 2017 Sep 8.

DOI:10.1016/j.lfs.2017.08.032
PMID:28893640
Abstract

AIMS

Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats.

MAIN METHODS

Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry.

KEY FINDINGS

The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well.

SIGNIFICANCE

Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress.

摘要

目的

氧化应激和炎症反应是导致肠道缺血再灌注(I/R)时多种组织损伤的主要因素。据报道,胍丁胺可减轻各种器官的I/R损伤。本研究旨在分析胍丁胺对大鼠肠道I/R损伤可能的保护作用。

主要方法

设计四组:假手术对照组、胍丁胺处理对照组、I/R对照组和胍丁胺处理I/R组。通过肠系膜上动脉闭塞半小时,随后进行3小时再灌注诱导小肠I/R损伤。在再灌注期前腹腔注射胍丁胺(10mg/kg)。再灌注180分钟后,在离体器官浴中检测对卡巴胆碱和氯化钾(KCl)的收缩反应。测定肠道组织中的丙二醛(MDA)、还原型谷胱甘肽(GSH)和髓过氧化物酶(MPO)活性。测定血浆细胞因子水平。还通过免疫组织化学评估肠道诱导型一氧化氮合酶(iNOS)的表达。

主要发现

胍丁胺治疗除了能恢复GSH含量外,似乎还能显著有效降低MDA含量和MPO活性。该治疗还减轻了组织学损伤。I/R诱导的iNOS、IFN-γ和IL-1α表达增加也通过该治疗恢复到假手术对照组水平。

意义

我们的研究结果表明,胍丁胺预处理可能主要通过减轻炎症反应和氧化应激来改善小肠再灌注诱导的损伤。

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