西南医科大学学报2024，Vol.47Issue(1)：39-44,6.DOI:10.3969/j.issn.2096-3351.2024.01.009
小胶质细胞PTGS2/Hepcidin炎症通路在神经元铁死亡中的作用机制
Microglia PTGS2/Hepcidin inflammatory pathway mediates ferroptosis of neurons
摘要
Abstract
Objective To investigate the regulation of ferroptosis in HT22 hippocampal neurons by BV2 microglia prostaglandin-endoperoxide synthase 2(PTGS2)and its underlying molecular mechanism.Methods BV-2 cells were cultured by using DMEM and divided into the model group(CELE group,CELE+LPS group and LPS group)and the control group.The inflammation model of BV2 microglia and the inhibition model of PTGS2 were established by lipopolysaccharide(LPS)and the selective PTGS2 inhibitor cele-coxib.HT22 neurons were incubated with the supernatant of the model medium.MTT assay was used to detect cell viability,and ELISA assay was used to detect oxidative stress and inflammatory factors.Iron concentration in neurons was determined by colorimetry.West-ern blotting and qPCR were used to detect the expression of related proteins and mRNA.Results After LPS treatment,the microglia ac-tivation markersIBA-1 and PTGS2 were increased in BV2 cells,and the expressions of inflammatory factors TNF-α,IL-1β and IL-6 in the supernatant of the culture medium were increased,which had statistical significance compared with the control group(P<0.01).PTSG2,TNF-α,IL-1β,and IL-6 expression was decreased in the CELE+LPS group,and the difference was statistically significant compared with that in the LPS group(P<0.05).Cell viability decreased,concentration of MDA and Fe2+,expression of ferroportin 1(FPN1),hepcidin and STAT3 phosphorylation(p-STAT3)were increased in HT22 cells of LPS group,which was statistically signifi-cant compared with the control group(P<0.01).In CELE+LPS group,cell viability was increased,the level of ferroptosis,FPN1,hep-cidin and p-STAT3 were decreased in HT22 cells.Conclusion Microglia PTGS2 up-regulated cellular inflammation and promoted fer-roptosis in neurons.The mechanism might be related to the promotion of STAT3 phosphorylation by PTGS2,the increase of hepcidin ex-pression,and the induction of iron homeostasis imbalance in neurons.关键词
铁死亡/小胶质细胞/前列腺素内过氧化物酶2/铁调素/铁稳态Key words
Ferroptosis/Microglia/Prostaglandin-endoperoxide synthase 2/Hepcidin/Iron homeostasis分类
医药卫生引用本文复制引用
杨晓玲,何宗源,章琦鑫,王鱼浩,李雪莲,段晓霞..小胶质细胞PTGS2/Hepcidin炎症通路在神经元铁死亡中的作用机制[J].西南医科大学学报,2024,47(1):39-44,6.基金项目
四川省科技厅自然科学基金(2022NCFSC1360) （2022NCFSC1360）
四川省人力资源和社会保障厅留学人员科技活动择优资助项目(19058) （19058）
西南医科大学校级科研项目(2021ZKQN059) （2021ZKQN059）
省级大学生创新创业训练计划项目(S202210632220,S202210632307) （S202210632220,S202210632307）
泸州市科技计划项目(2023JYJ001) （2023JYJ001）
