江苏大学学报（医学版）2025，Vol.35Issue(5)：401-409,9.DOI:10.13312/j.issn.1671-7783.y240195
人脐带间充质干细胞来源外泌体通过抑制Bid改善急性心肌梗死后铁死亡损伤
Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate ferroptotic injury after acute myocardial infarction by inhibiting Bid
摘要
Abstract
Objective:To investigate the therapeutic effects of human umbilical cord mesenchymal stem cell derived exosomes(hucMSC-Exo)on acute myocardial infarction(AMI)and to elucidate the underlying mechanisms.Methods:Human umbilical cord mesenchymal stem cells(hucMSCs)were isolated and cultured.Exosomes were extracted from the culture media.AMI model was constructed by ligating the anterior descending branch of the coronary artery in mice.The mice were randomly divided into Sham,AMI,Exo and Fer-1 groups,and PBS,PBS,hucMSC-Exo and Ferrostatin-1 were injected into the marginal zone of the ischemic myocardium of each group,respectively.The levels of the antioxidants glutathione(GSH)content and malondialdehyde(MDA)content in mouse myocardial tissues measured by corresponding assay kits,and reactive oxygen species(ROS)levels detected by DHE probe were used to assess the severity of ferroptosis in mouse myocardial tissue;Cardiac ultrasound and Masson staining were used to evaluate the cardiac function and fibrosis level in mice;HL-1 cells were treated with DMSO,Erastin and hucMSC-Exo and subjected to RNA sequencing,and the potential mechanism of the therapeutic effect of hucMSC-Exo was evaluated by KEGG enrichment analysis and clustering heat map analysis.The viability of HL-1 cells after hucMSC-Exo or hucMSC-Exo+BI-6C9 co-treatment was detected by CCK-8 assay.BH3 interacting domain death agonist(Bid)expression levels in infarcted myocardial tissues of mice were detected by qRT-PCR.Results:Compared with the AMI group,the Exo and Fer-1 groups of mice showed a significant decrease in MDA and ROS levels in the infarcted region of the myocardium,an increase in GSH content,a reduction in myocardial fibrosis,and an improvement in cardiac function;among the mice in the Exo group,the treatment effect was more pronounced compared to the Fer-1 group on the 28th day after AMI.KEGG enrichment analysis showed that the reversed genes by hucMSC-Exo were mainly enriched in the p53 signaling pathway;clustering heatmap analysis of p53-related genes revealed that Bid gene expression was significantly higher in HL-1 cells in the Erastin group compared with the control group,and the level of Bid expression in HL-1 cells in the Exo group was significantly lower than that in the Erastin group.The therapeutic effect of hucMSC-Exo in HL-1 cells was not significantly increased after treatment with the Bid inhibitor BI-6C9.Bid mRNA level in the heart tissues of mice in the AMI group was substantially increased compared with that in the control group,and was significantly decreased in the Exo group compared with that in the AMI group.Conclusion:hucMSC-Exo inhibits Bid expression to mitigate ferroptosis after AMI,thereby alleviate myocardial injury.关键词
急性心肌梗死/人脐带间充质干细胞来源的外泌体/铁死亡/BH3相互作用结构域死亡激动剂(Bid)Key words
acute myocardial infarction/human umbilical cord mesenchymal stem cell derived exosome/ferroptosis/BH3-interaction domain death agonist(Bid)分类
医药卫生引用本文复制引用
孙琅,彭伟,沈晗,余云生,陈一欢,陈磊,丁英龙,陈月秋,沈振亚..人脐带间充质干细胞来源外泌体通过抑制Bid改善急性心肌梗死后铁死亡损伤[J].江苏大学学报（医学版）,2025,35(5):401-409,9.基金项目
国家自然科学基金重点项目(92168203,82241201,82241202) （92168203,82241201,82241202）
