D-GalN/LPS诱导的急性肝衰竭小鼠肝组织cGAS-STING通路基因水平变化*

doi:10.3969/j.issn.1672-5069.2026.04.002

实用肝脏病杂志 ›› 2026, Vol. 29 ›› Issue (4): 485-488.doi: 10.3969/j.issn.1672-5069.2026.04.002

D-GalN/LPS诱导的急性肝衰竭小鼠肝组织cGAS-STING通路基因水平变化^*

林静, 贾纪会, 段钟平, 陈煜, 张晓慧

100069 北京市首都医科大学附属北京佑安医院肝病中心四科/肝再生与人工肝转化研究北京市重点实验室(林静,贾纪会,段钟平,陈煜);首都医科大学附属北京佑安医院北京肝病研究所(张晓慧)

收稿日期:2025-11-03 出版日期:2026-07-10 发布日期:2026-07-20
通讯作者: 张晓慧,E-mail:xiaohui.zhang@ccmu.edu.cn
作者简介:林静,女,24岁,硕士研究生。E-mail:19924463662@163.com
基金资助:
^*国家自然科学基金项目(编号:82470606);北京市高层次公共卫生技术人才建设项目(编号:学科骨干-02-24);首都医科大学附属北京佑安医院人才库培养计划项目(编号:YARCKC2022004);北京肝胆相照公益基金会力肝专项(编号:iGandanF-1082024-LG021);北京市自然科学基金资助项目(编号:7202070);首都卫生发展科研专项项目(编号:首发 2024-1-2181);北京肝病研究所改革与发展计划项目(编号:2025Y-KF-Q08)

cGAS-STING pathway is involved in regulating the development of D-GalN/LPS-induced acute liver failure in mice

Lin Jing, Jia Jihui, Duan Zhongping, et al

Fourth Department of Liver Disease, You’an Hospital, Capital Medical University, Beijing 100069, China

Received:2025-11-03 Online:2026-07-10 Published:2026-07-20

摘要/Abstract

摘要： 目的本研究旨在探究环磷酸鸟苷-磷酸腺苷合成酶(cGAS)/干扰素基因刺激因子(STING)通路对急性肝衰竭(ALF)的影响。方法随机将30只 C57BL/6J小鼠分为对照组、ALF组和C-176干预组,每组10只,采用D-氨基半乳糖 (D-GalN) 和脂多糖 (LPS) 联合腹腔注射诱导小鼠ALF模型,给予STING抑制剂(C-176)干预。采用qRT-PCR法检测肝组织基因水平。结果与ALF组比,C-176干预组小鼠生存时间明显延长(P<0.05); ALF组小鼠肝细胞大片坏死,排列紊乱,而C-176干预组小鼠肝细胞排列趋于规整,坏死灶减少;ALF组小鼠肝组织STING通路相关蛋白表达和基因水平显著升高,而C-176干预组小鼠则显著降低;C-176干预组小鼠肝组织IFN-Ⅰ、IL-1β、IL-6和TNF-α水平均显著低于ALF组(P<0.05),F4/80、CD4、CD8、Gr1、NK1.1和CD11c基因均显著下调,提示肝组织局部炎症反应得到明显的缓解(P<0.05)。结论 STING通路参与ALF的发生发展,抑制该信号通路可减轻ALF动物炎症介导的肝损伤。

关键词: 急性肝衰竭, 环磷酸鸟苷-磷酸腺苷合成酶/干扰素基因刺激因子通路, 细胞因子风暴, 小鼠

Abstract: Objective The aim of this experiment was to investigate the effect of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon gene (STING) pathway on ALF in vivo. Methods Thirty C57BL/6J mice were randomly assigned into control, model and intervention group, with 10 mice in each. Model was established by intraperitoneal injection of D-GalN/LPS, intervened by specific inhibitor C-176 and gene RNA was detected by qRT-PCR. Results Compared to in the model group, the C-176 intervention group exhibited a significant prolonged survival time (P<0.05); extensive hepatocellular necrosis and disordered architecture was found in the model group, whereas the liver tissue structure in the C-176 intervention group appeared more organized with reduced necrotic areas; immunohistochemistry and gene analysis demonstrated that the protein expression and mRNA levels of key components in the STING signaling pathway were significantly upregulated in the model group, but were notably downregulated in the C-176 intervention group; furthermore, IFN-Ⅰ, IL-1β, IL-6, TNF-α and F4/80, CD4, CD8, Gr1, NK1.1 and CD11c significantly decreased in the STING intervention group compared to the those in model group (P<0.05). Conclusion The STING pathway is involved in the inflammatory storm associated with ALF occurrence, and inhibition of this signaling pathway might alleviate immune-mediated liver injury in ALF.

Key words: Acute liver failure, cyclic guanosine monophosphate-adenosine monophosphate synthase /stimulator of interferon gene pathway, Cytokine storm, Mice

林静, 贾纪会, 段钟平, 陈煜, 张晓慧. D-GalN/LPS诱导的急性肝衰竭小鼠肝组织cGAS-STING通路基因水平变化^*[J]. 实用肝脏病杂志, 2026, 29(4): 485-488.

Lin Jing, Jia Jihui, Duan Zhongping, et al. cGAS-STING pathway is involved in regulating the development of D-GalN/LPS-induced acute liver failure in mice[J]. Journal of Practical Hepatology, 2026, 29(4): 485-488.

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D-GalN/LPS诱导的急性肝衰竭小鼠肝组织cGAS-STING通路基因水平变化^*

cGAS-STING pathway is involved in regulating the development of D-GalN/LPS-induced acute liver failure in mice

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