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丁酸钠抑制小鼠高迁移率族蛋白B1的表达与释放并减轻刀豆蛋白A诱导的急性肝损伤

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

作者信息

Gong Quan, Chen Mao-Jian, Wang Chao, Nie Hao, Zhang Yan-Xiang, Shu Ke-Gang, Li Gang

机构信息

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

出版信息

Sheng Li Xue Bao. 2014 Oct 25;66(5):619-24.

PMID:25332009
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.

摘要

本研究的目的是探讨丁酸钠(SB)预处理对刀豆蛋白A(Con A)诱导的小鼠急性肝损伤的保护作用。首先给模型动物腹腔注射SB。半小时后,通过尾静脉注射Con A(15 mg/kg)建立急性肝损伤小鼠模型。然后,使用自动化学分析仪通过标准临床方法测量血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,通过酶联免疫吸附测定法(ELISA)测量肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ),并使用苏木精-伊红(HE)染色和光学显微镜观察肝组织的病理变化。通过逆转录聚合酶链反应(RT-PCR)、免疫组织化学和ELISA评估高迁移率族蛋白B1(HMGB1)的表达和释放。结果表明,SB预处理显著保护Con A处理的小鼠免受肝损伤,血清ALT、AST降低(P < 0.01)以及肝组织坏死减少证明了这一点。SB还降低了血清TNF-α和IFN-γ水平(P < 0.01)。此外,SB预处理显著抑制了HMGB1的表达和释放(P < 0.05或P < 0.01)。这些结果表明,SB对Con A诱导的急性肝损伤的减轻作用可能归因于其降低TNF-α和IFN-γ产生以及抑制HMGB1表达和释放的作用。

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