中国药理学通报2025，Vol.41Issue(10)：1884-1892,9.DOI:10.12360/CPB202502008
转录因子FoxO1对肾脏缺血/再灌注损伤中铁死亡的影响
Mechanism of transcription factor FoxO1 on ferroptosis in renal ischemia-reperfusion injury
摘要
Abstract
Aim To investigate the effects of tran-scription factor FoxO1 on acute kidney injury(AKI)induced by ischemic reperfusion injury(IRI)and to explore the underlying mechanisms.Methods Male C57BL/6 mice were randomly divided into four groups:Sham,IRI,FoxO1 inducible cell-specific knockout(FoxO1 icKO),and IRI+FoxO1 icKO.Tamoxifen(25 mg·kg-1)was intraperitoneally injec-ted to specifically knock out FoxO1 in mouse macro-phages,and a unilateral renal IRI model was estab-lished.The levels of serum creatinine(Scr),blood u-rea nitrogen(BUN),Fe2+,malondialdehyde(MDA),reactive oxygen species(ROS),and reduced glutathi-one(GSH)in renal tissues were detected.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in renal tissues.Quantitative polymer-ase chain reaction(qPCR)was used to detect the mR-NA levels of inflammatory factors such as IL-1β and MCP1 in renal tissues.Western blot was used to detect the expression levels of apoptosis and ferroptosis-relat-ed proteins.Results Compared with the control group,the levels of Scr and BUN in the IRI group were significantly upregulated,the infiltration of inflammato-ry factors IL-1β,TNF-α and MCP1 increased,the pro-tein expressions of Bax/Bc12,cleaved-caspase-3/caspase-3,cytochrome C,and FTH1 in renal tissues were significantly enhanced,while the expression of GPX4 decreased.In addition,the levels of Fe2+,MDA and ROS in the renal cortex of the IRI group signifi-cantly increased,and the level of GSH markedly de-creased(P＜0.05).Compared with the IRI group,the levels of Scr and BUN in the FoxO1 icKO group were significantly reduced,the infiltration of inflammatory factors was alleviated,the expression of apoptosis-relat-ed proteins in renal tissue decreased,the expression level of ferroptosis protein GPX4 increased,and the ex-pression of FTH1 decreased.The levels of Fe2+,MDA and ROS in the renal cortex decreased,and the level of GSH significantly increased(P＜0.05).Conclusion Inducing the specific knockout of FoxO1 in macro-phages can alleviate AKI induced by IRI,and its mech-anism may be related to the inhibition of ferroptosis caused by IRI by FoxO1.关键词
急性肾损伤/缺血/再灌注损伤/铁死亡/巨噬细胞/转录因子/FoxO1Key words
acute kidney injury/renal ischemia-reperfusion injury/ferroptosis/macrophages/tran-scription factor/FoxO1分类
医药卫生引用本文复制引用
邓敏,杨雪,何瑶,祝贺杰,铁璐,李琳琳..转录因子FoxO1对肾脏缺血/再灌注损伤中铁死亡的影响[J].中国药理学通报,2025,41(10):1884-1892,9.基金项目
新疆维吾尔自治区重点研发项目(No 2023B02010) （No 2023B02010）
