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亚硝酸钠预处理对急性酒精损伤的小鼠肝脏的保护作用

路晓霞, 王思谦, 张挚, 徐红瑞, 刘彬, 皇甫超申^*

河南大学 医学院环境医学研究所；护理学院，开封 475004

摘要

本文旨在研究亚硝酸钠预处理对急性酒精损伤小鼠肝脏的保护作用。将40只C57bL/6 小鼠随机分为4组：急性酒精肝损伤组腹腔注射乙醇(4.5 g/kg)；亚硝酸钠预处理组腹腔注射亚硝酸钠(16 mg/kg) 12 h后，再给予乙醇(4.5 g/kg)；对照组仅给予生理盐水；单纯亚硝酸钠组仅给予亚硝酸钠(16 mg/kg)。处理结束时检测肝脏指数，比色法检测肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性，丙二醛(MDA)含量及血清丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)活性，HE和荧光标记TUNEL染色观察肝组织病理学改变，免疫组织化学染色法和Western blot检测缺氧诱导因子-1α (HIF-1α)蛋白表达。结果显示，与急性酒精肝损伤组相比，亚硝酸钠预处理组肝脏指数、血清ALT和AST活性显著下降，急性酒精损伤引起的小鼠肝组织病理学变化得到改善，坏死程度明显减轻，肝组织SOD、GSH-Px、CAT活性增加，MDA含量和细胞凋亡指数降低，肝细胞内HIF-1α蛋白表达水平显著升高。以上结果提示，亚硝酸钠预处理可减轻急性酒精肝损伤，其机制涉及氧化应激的抑制和HIF-1α蛋白水平的上调。

关键词： 亚硝酸钠; 预处理; 酒精性肝损伤; 抗氧化; 缺氧诱导因子-1α

分类号：R363

[Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice.] [Article in Chinese]

LU Xiao-Xia, WANG Si-Qian, ZHANG Zhi, XU Hong-Rui, LIU Bin, HUANGFU Chao-Shen^*

The Institute of Environmental Medicine, Medical College； Nursing College, Henan University, Kaifeng 475004, China

Abstract

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.

Key words: sodium nitrite; preconditioning; alcoholic liver injury; antioxidation; hypoxia-inducible factor-1α

收稿日期：2011-11-07　　录用日期：2012-01-11

通讯作者：皇甫超申　　E-mail: chaoshen6403@henu.edu.cn

引用本文：

路晓霞, 王思谦, 张挚, 徐红瑞, 刘彬, 皇甫超申. 亚硝酸钠预处理对急性酒精损伤的小鼠肝脏的保护作用[J]. 生理学报 2012; 64 (3): 313-320.

LU Xiao-Xia, WANG Si-Qian, ZHANG Zhi, XU Hong-Rui, LIU Bin, HUANGFU Chao-Shen. [Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (3): 313-320 (in Chinese with English abstract).