山西医科大学学报2025,Vol.56Issue(12):1349-1356,8.DOI:10.13753/j.issn.1007-6611.2025.12.004
间充质干细胞对海马神经细胞缺氧复氧损伤的影响及机制
Effect and mechanism of mesenchymal stem cells on hypoxia-reoxygenation injury in hippocampal neurons
摘要
Abstract
Objective To investigate the effect and mechanism of mesenchymal stem cells(MSCs)on hippocampal neuronal injury induced by hypoxia/reoxygenation(H/R).Methods Hippocampal neurons were divided into three groups:control group,H/R group,and MSCs co-culture group.Cell viability was detected by CCK-8 kit.The levels of glutathione(GSH),Caspase-3,Fe²⁺,and malondialdehyde(MDA)were measured by ELISA.The content of reactive oxygen species(ROS)and the cell apoptosis were detected by flow cytometry.The expression levels of glutathione peroxidase 4(GPX4)and transferrin receptor(TFR)were detected by Western blot.To further clarify whether MSCs exert neuroprotective effects by regulating the ferroptosis pathway,ferroptosis inhibitor Liprox-statin-1(Lip-1)and agonist Erastin were used for intervention,and the cells were divided into:H/R group,MSCs group,Lip-1 group,and MSCs+Lip-1 group;or H/R group,MSCs group,Erastin group,and MSCs+Erastin group.Then cell viability,and ferrop-tosis-related indicators such as GSH,Fe2+,and MDA were measured.Results Compared with control group,the levels of ROS,MDA,and Fe²⁺,and the activity of Caspase-3 were significantly increased in H/R group(P<0.01),the content of GSH and the cell viability were significantly decreased(P<0.01);meanwhile,GPX4 expression was significantly down-regulated(P<0.01),and TFR expression was significantly up-regulated(P<0.01).Compared with H/R group,the levels of ROS,MDA,and Fe²⁺,and the cell apop-tosis were significantly reduced in MSCs group(P<0.05),and GSH content and the cell viability were increased(P<0.05);GPX4 expression was significantly up-regulated(P<0.05),while TFR expression was significantly down-regulated(P<0.01).Compared with H/R group,the cell viability,and GSH content were significantly increased in Lip-1 group(P<0.01),GPX4 expression was up-regu-lated(P<0.05),TFR expression was down-regulated(P<0.01),and the contents of MDA and Fe²⁺ were reduced(P<0.01).Compared with MSCs group,GPX4 expression was significantly up-regulated while TFR expression was down-regulated in MSCs+Lip-1 group(P<0.01),the contents of MDA and Fe²⁺ were reduced(P<0.01),and there was no significant difference in the cell viability and GSH content.Compared with H/R group,the cell viability and GSH content were significantly decreased in Erastin intervention group(P<0.05),and the contents of MDA and Fe²⁺ were increased(P<0.01).Ccompared with MSCs group,the cell viability and GSH content were significantly decreased in MSCs+Erastin group(P<0.05),and the contents of MDA and Fe²⁺ were increased(P<0.01).Conclusion MSCs exert a role in cell repair by inhibiting ferroptosis in hippocampal neurons after hypoxia/reoxygenation.关键词
间充质干细胞/海马神经细胞/铁死亡/缺氧复氧损伤/氧化应激/细胞修复Key words
mesenchymal stem cells/hippocampal neurons/ferroptosis/hypoxia-reoxygenation injury/oxidative stress/cell repair分类
医药卫生引用本文复制引用
MENG Yuancui,ZHU Yanping..间充质干细胞对海马神经细胞缺氧复氧损伤的影响及机制[J].山西医科大学学报,2025,56(12):1349-1356,8.基金项目
国家自然科学基金资助项目(82060288) (82060288)