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OA

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.