实用肝脏病杂志2026，Vol.29Issue(5)：649-652,4.DOI:10.3969/j.issn.1672-5069.2026.05.003
LPS/D-gal诱导急性肝衰竭小鼠肝组织cGAS-STING通路蛋白表达及其肝素保护作用研究
Hepatic tissue of cGAS-STING pathway proteins and heparin's protective roles in LPS/D-gal-induced acute liver failure in mice
罗轲 1张丹眉 1郭金 1龚作炯1
作者信息
- 1. 430060 湖北省武汉市 武汉大学人民医院感染病科
- 折叠
摘要
Abstract
Objective This experiment aimed to investigate the effects of extracellular histones and heparin intervention on cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in mice with lipopolysaccharide(LPS)/D-galactosamine(D-gal)-induced acute liver failure(ALF).Methods Forty mice were randomly divided into control,model,extracellular histones-intervened and extracellular histones/heparin-intervened groups,with 10 mice in each.ALF model was established in mice by using LPS/D-gal intraperitoneal injection.Hepatic protein expression of cGAS and STING were detected by Western blotting,and hepatic homogenate tumor necrosis factor-α(TNF-α),interleukin(IL)-1 β and IL-18 levers were measured by using ELISA.Results Histopathological examination of liver tissue confirmed the successful establishment of ALF model in mice,liver tissue damage in the extracellular histones-intervened group was similar to that in the model group,whereas it was significantly milder in the extracellular histones/heparin-intervened group;serum ALT and AST levels in the model group and extracellular histones group were significantly higher than those in the control group(P＜0.05),while they decreased greatly in the extracellular histones/heparin-intervened group(P＜0.05);hepatic cGAS and STING expression,and liver tissue homogenate TNF-α,IL-1 β and IL-18 levels in the model group and extracellular histones group were significantly intensified and elevated as compared to in the control group(P＜0.05),however,the expression or levels of these molecules in the extracellular histones/heparin group were significantly weaken or reduced compared to both in the model group or in the extracellular histones group(P＜0.05).Conclusion Extracellular histones could induce ALF,probably by activating the cGAS-STING pathway,while heparin might inhibit extracellular histone expression and block the cGAS-STING pathway and thereby exerting a protective effect.关键词
急性肝衰竭/胞外组蛋白/肝素/环鸟苷酸-腺苷酸合成酶-干扰素刺激因子通路/小鼠Key words
Acute liver failure/Extracellular histone/Heparin/cyclic GMP-AMP synthase-stimulator of interferon genes/Mice引用本文复制引用
罗轲,张丹眉,郭金,龚作炯..LPS/D-gal诱导急性肝衰竭小鼠肝组织cGAS-STING通路蛋白表达及其肝素保护作用研究[J].实用肝脏病杂志,2026,29(5):649-652,4.
