医学分子生物学杂志2026，Vol.23Issue(3)：242-249,8.DOI:10.3870/j.issn.1672-8009.2026.03.002
GPER通过阻断氧化应激-炎症恶性循环改善内毒素诱导肝细胞损伤的机制研究
The Protective Role of GPER Against Endotoxin-Induced Hepatocyte Injury via Disruption of Oxidative Stress-Inflammation Cycle
摘要
Abstract
Objective To investigate the protective effect of the G protein-coupled estrogen re-ceptor(GPER)against endotoxin-induced hepatocyte injury and its underlying molecular mecha-nism,and to evaluate its potential as a sex-specific therapeutic strategy.Methods An AML-12 mouse hepatocyte model induced by lipopolysaccharide(LPS)was used to simulate the early path-ological processes of septic liver injury.The cells were divided into four groups:blank control,LPS,LPS+G1(a GPER agonist),and LPS+G15(a GPER antagonist).Techniques including flow cytometry,Western blot,RT-qPCR,ELISA,and transmission electron microscopy were em-ployed to assess apoptosis rate,GPER expression,mtROS,MDA,NLRP3 inflammasome activa-tion,IL-1β levels,ATP/AMP ratio,ΔΨm,and ultrastructural changes.Results Compared with the LPS group,G1 treatment significantly reduced the apoptosis rate,suppressed mtROS and MDA production,downregulated the NLRP3/Caspase-1/IL-1β signaling pathway,increased ATP level,decreased the AMP/ATP ratio,and ameliorated mitochondrial membrane potential and ultrastruc-ture.In contrast,G15 exacerbated these injuries.Correlation analysis showed that GPER expression was negatively correlated with the apoptosis rate(R2=0.8970),while mtROS levels were positive-ly correlated with both apoptosis rate and IL-1β content.Conclusion GPER activation alleviates septic liver injury by inhibiting mtROS production,blocking NLRP3 inflammasome activation and subsequent inflammatory responses,and improving mitochondrial energy metabolism and structural integrity.This mechanism provides a novel target and theoretical basis for sex-specific treatment strat-egies in clinical practice.关键词
脓毒症肝损伤/G 蛋白偶联雌激素受体/氧化应激/NLRP3炎症小体/线粒体功能障碍/性别差异Key words
septic liver injury/G protein-coupled estrogen receptor/oxidative stress/NL-RP3 inflammasome/mitochondrial dysfunction/gender difference分类
医药卫生引用本文复制引用
杨镭镭,彭坚,冯小静,高珊,陈真..GPER通过阻断氧化应激-炎症恶性循环改善内毒素诱导肝细胞损伤的机制研究[J].医学分子生物学杂志,2026,23(3):242-249,8.基金项目
湖北省自然科学基金计划(No.2023AFC030) This work was supported by a grant from the Natural Science Foundation of Hubei Province(No.2023AFC030). （No.2023AFC030）
