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正丁酸钠通过抑制高迁移率族蛋白B1的表达与释放减轻刀豆蛋白A诱导的小鼠急性肝损伤

龚权^*, 陈茂剑, 王超, 聂浩, 张燕翔, 舒克钢, 李刚

长江大学医学院病原生物学部，荆州 434023

摘要

本文旨在研究正丁酸钠预处理对刀豆蛋白A (concanavalin A, Con A)诱导的小鼠急性肝损伤的保护作用及机制。给小鼠腹腔注射正丁酸钠(500 mg/kg) 0.5 h后，尾静脉注射Con A (15 mg/kg)诱导小鼠急性肝损伤模型，测定小鼠血清谷丙转氨酶(alanine aminotransferase, ALT)、谷草转氨酶(aspartate aminotransferase, AST) 的水平；HE染色观察病理学改变；ELISA法检测血清肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)、干扰素-γ (interferon-γ, IFN-γ)和高迁移率族蛋白B1 (high-mobility group box 1, HMGB1)水平；RT-PCR和免疫组化法检测小鼠肝组织HMBG1的表达与释放。结果显示，正丁酸钠预处理能明显降低Con A诱导的急性肝损伤小鼠血清中ALT和AST水平(P < 0.01)；显著改善肝组织损伤程度；明显降低血清中TNF-α和IFN-γ的水平(P < 0.01)；显著抑制肝组织HMGB1的表达与释放(P < 0.05或P < 0.01)。以上结果提示，正丁酸钠预处理对Con A所诱导的小鼠急性肝损伤具有保护作用，可能与其减少炎性细胞因子TNF-α和IFN-γ的产生及抑制HMGB1的表达与释放有关。

关键词： 正丁酸钠; 刀豆蛋白A; 急性肝损伤; 肿瘤坏死因子-α; 干扰素-γ; 高迁移率族蛋白B1

分类号：R392.5

[Sodium butyrate inhibits HMGB1 expression and release and attenuates concanavalin A-induced acute liver injury in mice.] [Article in Chinese]

GONG Quan^*, CHEN Mao-Jian, WANG Chao, NIE Hao, ZHANG Yan-Xiang, SHU Ke-Gang, LI Gang

Department of Pathogen Biology, School of Medicine, Yangtze University, Jingzhou 434023, China

Abstract

The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.

Key words: sodium butyrate; concanavalin A; acute liver injury; TNF-α; IFN-γ; high-mobility group box 1

收稿日期：2014-04-17　　录用日期：2014-06-03

通讯作者：龚权　　E-mail: gongquan1998@163.com

引用本文：

龚权, 陈茂剑, 王超, 聂浩, 张燕翔, 舒克钢, 李刚. 正丁酸钠通过抑制高迁移率族蛋白B1的表达与释放减轻刀豆蛋白A诱导的小鼠急性肝损伤[J]. 生理学报 2014; 66 (5): 619-624.

GONG Quan, CHEN Mao-Jian, WANG Chao, NIE Hao, ZHANG Yan-Xiang, SHU Ke-Gang, LI Gang. [Sodium butyrate inhibits HMGB1 expression and release and attenuates concanavalin A-induced acute liver injury in mice.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (5): 619-624 (in Chinese with English abstract).