浙江医学2025，Vol.47Issue(14)：1472-1476,后插2,6.DOI:10.12056/j.issn.1006-2785.2025.47.14.2024-2339
艾司氯胺酮调控HIF-1α/HO-1信号通路对脂多糖诱导的小鼠肺泡上皮细胞铁死亡的影响
Effects of esketamine on ferroptosis of mouse alveolar epithelial cells induced by lipopolysaccharide through regulation of the HIF-1α/HO-1 signaling pathway
摘要
Abstract
Objective To investigate the effect of esketamine(Esket)on lipopolysaccharide(LPS)-induced mouse alveolar epithelial cell ferroptosis by regulating the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1)signaling pathway.Methods MLE-12 mouse alveolar epithelial cells were treated with 10 μg/mL LPS to establish an in vitro model of endotoxic acute lung injury.MLE-12 cells were divided into the following groups:Control group,LPS group(treated with 10 μg/mL LPS),LPS+Esket group(treated with 25 μmol/L Esket and 10 μg/mL LPS),HIF-1α small interfering RNA(siRNA)+LPS+Esket group(cells transfected with HIF-1α siRNA followed by treatment with 25 μmol/L Esket and 10 μg/mL LPS),HO-1 siRNA+LPS+Esket group(cells transfected with HO-1 siRNA followed by treatment of 25 μmol/L Esket and 10 μg/mL LPS),and negative control(NC)siRNA+LPS+Esket group(cells transfected with NC siRNA followed by treatment of 25 μmol/L Esket and 10 μg/mL LPS).Enzyme-linked immunosorbent assay was used to detect the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Reduced glutathione(GSH)and oxidized glutathione(GSSG)kits were used to detect cellular GSH and GSSG levels.FerroOrange kit was used to detect cellular ferrous ion(Fe2+)levels.Western blot was performed to detect the protein expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),HIF-1α,and HO-1.Results Compared with the Control group,the levels of IL-6,TNF-α,GSSG,and Fe2+in the LPS group,LPS+Esket group,and NC siRNA+LPS+Esket group were all increased,while the GSH level and the protein expression levels of GPX4 and SLC7A11 were decreased(all P＜0.05).Compared with the LPS group,the levels of IL-6,TNF-α,GSSG,and Fe2+in the LPS+Esket group and NC siRNA+LPS+Esket group were all decreased,while the GSH level and the protein expression levels of GPX4 and SLC7A11 were increased(all P＜0.05).Compared with the LPS+Esket group,the levels of IL-6,TNF-α,GSSG,and Fe2+in the HIF-1α siRNA+LPS+Esket group and HO-1 siRNA+LPS+Esket group were all increased,while the GSH level and the protein expression levels of GPX4 and SLC7A11 were decreased(all P＜0.05).Conclusion Esket inhibits ferroptosis of alveolar epithelial cells by regulating the HIF-1α/HO-1 signaling pathway,thereby alleviating inflammation and oxidative stress of alveolar epithelial cells caused by LPS.关键词
艾司氯胺酮/缺氧诱导因子-1α/血红素氧合酶-1信号通路/肺泡上皮细胞/脂多糖/铁死亡Key words
Esketamine/Hypoxia-inducible factor-1α/heme oxygenase-1 signaling pathway/Alveolar epithelial cells/Lipopolysaccharide/Ferroptosis引用本文复制引用
张继骁,马扬,王宝忠,钱程瑜,赵宇彤,田娜茜,王志学..艾司氯胺酮调控HIF-1α/HO-1信号通路对脂多糖诱导的小鼠肺泡上皮细胞铁死亡的影响[J].浙江医学,2025,47(14):1472-1476,后插2,6.基金项目
承德市基础研究项目(202204A157) （202204A157）
