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右美托咪定通过上调LC3-II表达减轻LPS/D-Gal诱导的急性肝损伤

何小姣¹, 谢彬², 黄崧^2,*, 刘明华²

¹武警重庆总队医院药剂科，重庆 400061；²陆军军医大学第一附属医院急救创伤中心，重庆 400038

摘要

本研究旨在探讨右美托咪定(dexmedetomidine, DEX)对脂多糖(lipopolysaccharide, LPS)/D-半乳糖胺(D-galactosamine, D-Gal)诱导的急性肝损伤的作用及其机制。给雄性BALB/c小鼠腹腔注射LPS和D-Gal诱导急性肝损伤，注射前30 min给予DEX或联合自噬抑制剂3-甲基腺嘌呤(3-methyladenine, 3-MA)预处理。用试剂盒测定血清丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)活性，以及肝组织髓过氧化物酶(myeloperoxidase, MPO)活性，用ELISA测定血清肿瘤坏死因子α (tumor necrosis factor α, TNF-α)和白细胞介素6 (interleukin-6, IL-6)水平，用Western blot检测肝组织P62、LC3-II蛋白表达水平，用HE染色观察肝组织病理学改变。结果显示，与对照组比较，LPS/D-Gal组血清ALT和AST活性升高，TNF-α和IL-6水平提高，肝组织MPO活性升高，LC3-II蛋白表达水平下调，P62蛋白表达水平下调，肝组织出现明显的病理损伤。DEX可逆转LPS/D-Gal组的上述变化，而3-MA可阻断DEX的这些肝保护效应。上述结果提示，DEX可减轻LPS/D-Gal诱导的急性肝损伤，这可能与上调LC3-II蛋白表达、激活自噬有关。

关键词： 右美托咪定; 脂多糖; 急性肝损伤; 自噬

分类号：R966

Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice

HE Xiao-Jiao¹, XIE Bin², HUANG Song^2,*, LIU Ming-Hua²

¹Department of Pharmacy, Chongqing Armed Corps Police Hospital, Chongqing 400061, China；²Center of Emergency and Trauma, First Affiliated Hospital of Army Medical University, Chongqing 400038, China

Abstract

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.

Key words: dexmedetomidine; lipopolysaccharide; acute liver injury; autophagy

收稿日期：2020-12-27　　录用日期：2021-06-03

通讯作者：黄崧　　E-mail: huangsong@cqmu.edu.cn

引用本文：

何小姣, 谢彬, 黄崧, 刘明华. 右美托咪定通过上调LC3-II表达减轻LPS/D-Gal诱导的急性肝损伤[J]. 生理学报 2021; 73 (6): 901-908.

HE Xiao-Jiao, XIE Bin, HUANG Song, LIU Ming-Hua. Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice. Acta Physiol Sin 2021; 73 (6): 901-908 (in Chinese with English abstract).