南方医科大学学报2025，Vol.45Issue(7)：1471-1478,8.DOI:10.12122/j.issn.1673-4254.2025.07.13
肝豆扶木汤通过GPX4/ACSL4/ALOX15通路抑制铁死亡改善Wilson病小鼠的肝脏脂肪变性
Gandou Fumu Decoction improves liver steatosis by inhibiting hepatocyte ferroptosis in mice with Wilson's disease through the GPX4/ACSL4/ALOX15 signaling pathway
摘要
Abstract
Objective To explore the mechanism of Gandou Fumu Decoction(GDFMD)for improving Wilson's disease(WD)in tx-J mice.Methods With 6 syngeneic wild-type mice as the control group,30 tx-J mice were randomized into WD model group,low-,medium-and high-dose GDFMD treatment groups,and Fer-1 treatment group.Saline(in control and model groups)and GDFMD(3.48,6.96 or 13.92 g/kg)were administered by gavage,and Fer-1 was injected intraperitoneally once daily for 14 days.Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue;ALT,AST,albumin,AKP levels were determined to assess liver function of the mice.Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4,ACSL4,ALOX15,FTH1,FLT,TFR1,FAS,SCD1,and ACOX1,and Fe2+,MDA,ROS,SOD,GSH and 4-HNE levels were analyzed to assess oxidative stress.Results The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT,AST and AKP,decreased albumin level,increased Fe2+,MDA,ROS,4-HNE levels,decreased SOD and GSH levels(P<0.05),lowered protein expressions of ACOX1,GPX4,FTH1,FLT,FAS,and SCD1,and increased protein contents of TFR1,ACSL4 and ALOX15 in the liver.Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models,decreased the levels of Fe2+,MDA and ROS,increased SOD and GSH levels,and reversed the changes in hepatic protein expressions.Conclusion GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.关键词
wilson病/肝豆状核变性/铁死亡/肝脏的脂肪变性Key words
Gandou Fumu Decoction/wilson's diseast/ferroptosis/steatosis of the liver引用本文复制引用
张梦影,赵晨玲,田丽伟,余郭芳,杨文明,董婷..肝豆扶木汤通过GPX4/ACSL4/ALOX15通路抑制铁死亡改善Wilson病小鼠的肝脏脂肪变性[J].南方医科大学学报,2025,45(7):1471-1478,8.基金项目
安徽省临床医学研究转化专项(202204295107020043) （202204295107020043）
安徽省高等学校科学研究项目(重点项目,2024AH051058) （重点项目,2024AH051058）
国家级大学生创新创业训练计划项目(202410369006X) （202410369006X）
