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

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

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30min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(alanineaminotransferase,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 factorα,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。

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 factorα(TNF-α)and interleukin-6(IL-6)levels were determined by ELISA.The protein expression levels of LC3-Ⅱand 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-αand IL-6 levels,as well as MPO activity,up-regulated LC3-Ⅱand 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-Ⅱprotein expression and the activation of autophagy.