海南医科大学学报2026，Vol.32Issue(17)：1290-1295,6.DOI:10.13210/j.cnki.jhmu.20251103.001
敲除LCN2基因抑制脓毒症小鼠肝脏cGAS-STING通路和铁自噬减轻铁死亡的发生
Knockout of LCN2 gene alleviates ferroptosis by inhibiting ferritinophagy and cGAS-STING pathway in the liver of septic mice
摘要
Abstract
Objective:To investigate the changes and mechanism of cGAS-STING pathway and ferritinophagy in ferroptosis of sepsis-induced liver injury in lipocalin-2(LCN2)gene knockout mice.Methods:A total of 36 SPF-grade male C57BL/6J mice were randomly divided into 4 groups:the sham surgery(WT)group,the cecal ligation and puncture(CLP)group,the LCN2 gene knockout(LCN2-/-)group,and the LCN2-/-with CLP treatment(LCN2-/-+CLP)group,with 9 in each group.After 24 hours of CLP modeling,liver tissue pathological changes were observed using H&E staining.The levels of serum alanine amino-transferase(ALT)and aspartate aminotransferase(AST),as well as the levels of liver malondialdehyde(MDA)and superoxide dismutase(SOD)were analyzed.Reactive oxygen species levels in liver tissue were assessed using the DHE probe.The protein expression levels of LCN2,GPX4,FTH1,NCOA4,LC3B,cGAS,and STING in liver tissues were detected by Western blot.Results:After CLP surgery,the result of H&E staining revealed balloon-like degeneration of hepatocytes and inflammatory cell infiltration in liver tissues,which were alleviated after LCN2 gene knockout.Compared to the WT group,the CLP group showed increased levels of ALT,AST,and MDA,and a decreased level of SOD(P<0.001),as well as decreased expression levels of GPX4 and FTH1 proteins in liver tissue,and increased expression levels of NCOA4,LC3BⅡ/LC3BⅠ,cGAS,and STING proteins(P<0.01).Compared to the CLP group,ALT,AST,and MDA levels decreased,SOD level increased(P<0.01);CPX4 and FTH1 protein expression levels increased,and NCOA4,LC3BⅡ/LC3BⅠ,cGAS,and STING protein expression levels decreased(P<0.05)in the LCN2-/-+CLP group.Conclusion:Knockout of the LCN2 gene alleviates ferroptosis in hepato-cytes of septic mice by inhibiting ferritinophagy and the cGAS-STING pathway.关键词
脂质运载蛋白2(LCN2)/铁自噬/脓毒症,铁死亡Key words
Lipocalin-2(LCN2)/Ferritinophagy/Sepsis/Ferroptosis分类
医药卫生引用本文复制引用
贺玉莹,张淋淋,张瑞,王奕人,李璐,王佳慧,叶红伟,高琴..敲除LCN2基因抑制脓毒症小鼠肝脏cGAS-STING通路和铁自噬减轻铁死亡的发生[J].海南医科大学学报,2026,32(17):1290-1295,6.基金项目
This study was supported by Excellent Scientific Research and Innovation Team of Universities in Anhui Province(2022AH010083) （2022AH010083）
National Natural Science Foundation Incubation Program of Bengbu Medical University(2024byfy004) （2024byfy004）
Research and Innovation Project of Bengbu Medical University(Byycx24001,Byycx22014) 安徽省高校优秀科研创新团队资助项目(2022AH010083) （Byycx24001,Byycx22014）
蚌埠医科大学国家自然科学基金孵育项目(2024byfy004) （2024byfy004）
蚌埠医科大学科研创新项目(Byycx24001,Byycx22014) （Byycx24001,Byycx22014）
