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过氧化氢酶抑制剂氨基三唑减轻急性酒精性肝损伤

艾青, 葛璞, 代洁, 梁天才, 杨青, 林玲, 张力

重庆医科大学生理学教研室；病理生理学教研室，重庆 400016；重庆文理学院校医院，重庆 402160

摘要

本文旨在通过观察过氧化氢酶(catalase, CAT)抑制剂氨基三唑(aminotriazole, ATZ)对酒精诱导的急性肝损伤的影响，初步探讨CAT在酒精性肝损伤中的可能作用。以雄性Sprague Dawley (SD)大鼠为实验对象，采用酒精腹腔注射诱导急性肝损伤，在造模前30 min腹腔注射 不同剂量ATZ (100~400 mg/kg)或相同体积溶剂(对照)。造模24 h后，检测大鼠血浆天冬氨酸转氨酶(aspartate transaminase, AST)、丙氨酸转氨酶(alanine transaminase, ALT)及乳酸脱氢酶(lactate dehydrogenase, LDH)水平，用HE染色法观察肝组织病理改变程度，用试剂盒检测肝组织内CAT活性、过氧化氢(hydrogen peroxide, H2O2)水平及丙二醛(malondialdehyde, MDA)含量，ELISA法检测血浆中肿瘤坏死因子α (tumor necrosis factor-α, TNF-α)及白介素-6 (interleukin-6, IL-6)水平。结果显示，ATZ处理可剂量依赖性降低酒精暴露大鼠血浆中ALT、AST及LDH水平，并减轻酒精诱导的肝组织病理损伤；ATZ可抑制酒精暴露大鼠肝组织内CAT活性、降低H2O2水平及MDA含量；ATZ也可下调酒精暴露大鼠血浆中TNF-α和IL-6水平。以上结果表明，ATZ可减轻酒精诱导的大鼠急性肝损伤，提示CAT可能在酒精性肝损伤中发挥了重要的致病作用。

关键词： 过氧化氢酶; 酒精性肝损伤; 氨基三唑; 氧化应激

分类号：R364.2;R575.1

[The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury.] [Article in Chinee]

AI Qing, GE Pu, DAI Jie, LIANG Tian-Cai, YANF Qing, LIN Ling, ZHANG Li

Department of Physiology； Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China； Hospital of Chongqing University of Arts and Sciences, Chongqing 402160, China

Abstract

In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100–400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H2O2) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H2O2 and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.

Key words: Catalase; alcoholic liver injury; aminotriazole; oxidative stress

收稿日期：2014-06-18　　录用日期：2014-08-25

通讯作者：张力　　E-mail: zhangli@cqmu.edu.cn

引用本文：

艾青, 葛璞, 代洁, 梁天才, 杨青, 林玲, 张力. 过氧化氢酶抑制剂氨基三唑减轻急性酒精性肝损伤[J]. 生理学报 2015; 67 (1): 97-102.

AI Qing, GE Pu, DAI Jie, LIANG Tian-Cai, YANF Qing, LIN Ling, ZHANG Li. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury.] [Article in Chinee]. Acta Physiol Sin 2015; 67 (1): 97-102 (in Chinese with English abstract).