中国医科大学学报2026，Vol.55Issue(1)：9-14,6.DOI:10.12007/j.issn.0258-4646.2026.01.002
自噬通过核受体共激活因子4调控代谢相关脂肪性肝病中肝细胞铁死亡的分子机制
Molecular mechanism of autophagy in modulating ferroptosis in metabolic associated fatty liver disease via nuclear receptor coactivator factor 4
摘要
Abstract
Objective To determine whether autophagy regulates ferroptosis in hepatocytes in metabolic associated fatty liver disease(MAFLD)via nuclear receptor coactivator factor 4(NCOA4).Methods L02 hepatocytes were treated with 1 mmol/L free fatty acid(FFA)to establish an in vitro MAFLD cell model and were divided into control,model,and chloroquine groups.The effectiveness of the model was evaluated using oil red O staining and the levels of triglyceride(TG),total cholesterol(TC),aspartate aminotransferase(AST),and ala-nine aminotransferase(ALT).Western blotting and quantitative real-time PCR were used to detect SLC7A11,GPX4,FTH1,TFR1,LC3B,LC3-Ⅱ/LC3-Ⅰ,ATG7,and NCOA4 expression in the hepatocytes from each group.Twelve C57BL/6 mice were randomly divided into control(WT)and model(HFCFD)groups.Mice in the HFCFD group were fed a high fat/cholesterol/fructose diet.Immunohistochemical staining was used to detect the expression of LC3B,NCOA4,FTH1,and SLC7A11 in mouse liver tissues.Results After FFA treatment,lipid droplets were found to accumulate in hepatocytes and the levels of TG,TC,AST,and ALT increased(P<0.05).In the model group,the expression of SLC7A11,GPX4,and FTH1 in the hepatocytes decreased(P<0.05),and the expression of TFR1,LC3-Ⅱ/LC3-Ⅰ,ATG7,and NCOA4 increased(P<0.05)compared to the control group.In the chloroquine group,the expression of SLC7A11,GPX4,and FTH1 in the hepatocytes decreased(P<0.05),and the expression of TFR1,LC3-Ⅱ/LC3-Ⅰ,ATG7,and NCOA4 increased(P<0.05)compared to the model group.In the HFCFD group,the expression of LC3B and NCOA4 in the mouse liver tissue increased(P<0.05),and the expression of FTH1 and SLC7A11 decreased(P<0.05)compared to the WT group.Conclusion Autophagy inhibits ferroptosis in liver cells in MAFLD by suppressing NCOA4 protein expression and reducing FTH1 degradation.关键词
肝细胞/铁死亡/自噬/核受体共激活因子4/代谢相关脂肪性肝病Key words
hepatocyte/ferroptosis/autophagy/nuclear receptor coactivator factor 4/metabolic associated fatty liver disease分类
医药卫生引用本文复制引用
高天,曹宇萌,张瑞昕,李倩倩,刘立新..自噬通过核受体共激活因子4调控代谢相关脂肪性肝病中肝细胞铁死亡的分子机制[J].中国医科大学学报,2026,55(1):9-14,6.基金项目
中央引导地方科技发展资金(YDZX20201400001965) （YDZX20201400001965）
