中国输血杂志2025，Vol.38Issue(8)：1008-1015,8.DOI:10.13303/j.cjbt.issn.1004-549x.2025.08.002
Ferrostatin-1通过抑制铁死亡减轻小鼠输血相关急性肺损伤
Ferrostatin-1 prevents transfusion-related acute lung injury in mice by inhibiting ferroptosis
摘要
Abstract
Objective To investigate the role of ferroptosis in transfusion-related acute lung injury(TRALI)and evalu-ate the efficacy of the specific inhibitor Ferrostatin-1(Fer-1),thereby to provide a basis for the prevention and treatment of TRALI.Methods This study utilized a"2-hit"model to induce TRALI in mice.The mouse model of TRALI was validated through survival curve analysis,lung tissue wet/dry weight ratio(W/D),myeloperoxidase(MPO)activity,and total pro-tein concentration in lung tissue.Samples from the TRALI model group,LPS group,and control group(n=6)were collect-ed.The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators,including iron concentra-tion in lung tissue,malondialdehyde(MDA)level,lipid peroxidation products(LPO)level,and expression levels of relat-ed proteins(GPX4,ACSL4).Additionally,a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects.The survival rates and clinical symptoms of the four groups(n=6)were dynamically monitored,and the degrees of lung injury were assessed.Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1.Results A mouse model of TRALI was successfully established.Compared to the control and LPS groups,the TRALI group showed significantly higher levels of ferrous iron[(18.32±1.11)nmol/well,MDA[(14.68±0.96)μmol/L],and LPO[(1.60±0.02)μmol/L]in lung tissue(all P<0.01),along with a downregulation of GPX4 and an upregulation of ACSL4.Fer-1 pretreatment significantly reversed these abnormalities:the W/D ratio decreased to 4.01±0.43,and MPO activity significantly decreased[Fer-1 group:(21 606±4 235)pg/mL vs TRALI group:(30 724±2 616)pg/mL],the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8%compared to the TRALI group(all P<0.01).These changes indicate that the lung injury in mice was alleviated after treatment.Following Fer-1 intervention,ferrous iron concentration[(7.46±1.83)nmol/well]was restored to a level close to that of the control group[(5.48±0.70)nmol/well].Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8%and 29.4%,respectively(P<0.001).Additionally,the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice(both P>0.05).Conclusion The progression of TRALI is closely related to the activa-tion of ferroptosis,characterized by iron overload,lipid peroxidation accumulation,and the imbalance of GPX4/ACSL4.Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway,sug-gesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.关键词
铁死亡/输血相关急性肺损伤/Ferrostatin-1/脂质过氧化/二次打击模型Key words
ferroptosis/transfusion-related acute lung injury/Ferrostatin-1/lipid peroxidation/2-hit model分类
医药卫生引用本文复制引用
刘思炜,肖玲,徐海霞,程佳乐,田力,刘忠..Ferrostatin-1通过抑制铁死亡减轻小鼠输血相关急性肺损伤[J].中国输血杂志,2025,38(8):1008-1015,8.基金项目
血液安全预警体系构建及干预研究(2024)(2021-I2M-1-060-2024-C0) （2024）
