首页|束缚应激致高脂血症ApoE-/-小鼠心肌损伤的分子靶标筛选与机制分析

束缚应激致高脂血症ApoE-/-小鼠心肌损伤的分子靶标筛选与机制分析

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目的 采用蛋白质组学技术筛选慢性束缚应激致高脂血症小鼠心肌损伤的标志物及其潜在机制.方法 通过束缚ApoE-/-小鼠建立高脂血症合并慢性应激模型,运用蛋白质组学与生物信息学等技术描绘慢性应激对高脂血症小鼠心肌损伤的特征性分子改变及相关调控机制,并从中探索潜在的诊断标志物.结果 蛋白质组学分析结果显示,与高脂血症组相比,高脂血症合并束缚应激组小鼠共有43个显著上调与58个显著下调的差异表达蛋白质.其中,GBP2、TAOK3、TFR1、UCP1是极具诊断潜力的分子标志物.KEGG通路富集分析结果表明,铁死亡是加剧高脂血症合并束缚应激模型心肌损伤的重要机制通路.mmu_circ_0001567/miR-7a/Tfr-1和mmu_circ_0001042/miR-7a/Tfr-1可能是该模型中与铁死亡相关的重要circRNA-miRNA-mRNA调控网络.结论 慢性束缚应激可能通过铁死亡加剧高脂血症小鼠的心肌损伤,本研究筛选出4个具有潜在应用价值的心肌损伤分子诊断标志物,为高脂血症合并应激致心脏性猝死的研究提供了新的方向.
Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/-Mice
Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

forensic pathologybioinformaticschronic restraint stresshyperlipidemiaferroptosisbio-markermyocardial injurymice

陈尚亨、董盛仲、王智敏、洪光辉、叶星、林子杰、林俊毅、江洁清、王守宇、林汉成、沈忆文

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复旦大学基础医学院法医学系,上海 200032

法医病理学 生物信息学 慢性束缚应激 高脂血症 铁死亡 生物标志物 心肌损伤 小鼠

国家重点研发计划

2018YFC0807202

2024

法医学杂志
司法部司法鉴定科学技术研究所

法医学杂志

CSTPCDCHSSCD北大核心
影响因子:0.32
ISSN:1004-5619
年,卷(期):2024.40(2)
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