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心肌缺血再灌注损伤中氧化应激相关基因的表达模式及分子机制

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia-Reperfusion Injury.

作者信息

Wu Jiahe, Luo Jingyi, Cai Huanhuan, Li Chenze, Lei Zhe, Lu Yi, Ni Lihua, Cao Jianlei, Cheng Bo, Hu Xiaorong

机构信息

Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Institute of Myocardial Injury and Repair, Wuhan University, Wuhan 430071, China.

出版信息

J Cardiovasc Dev Dis. 2023 Feb 13;10(2):79. doi: 10.3390/jcdd10020079.

Abstract

(1) Background: The molecular mechanism of oxidative stress-related genes (OSRGs) in myocardial ischemia-reperfusion injury (MIRI) has not been fully elucidated. (2) Methods: Differential expression analysis, enrichment analysis, and PPI analysis were performed on the MIRI-related datasets GSE160516 and GSE61592 to find key pathways and hub genes. OSRGs were obtained from the Molecular Signatures Database (MSigDB). The expression pattern and time changes of them were studied on the basis of their raw expression data. Corresponding online databases were used to predict miRNAs, transcription factors (TFs), and therapeutic drugs targeting common differentially expressed OSRGs. These identified OSRGs were further verified in the external dataset GSE4105 and H9C2 cell hypoxia-reoxygenation (HR) model. (3) Results: A total of 134 DEGs of MIRI were identified which were enriched in the pathways of "immune response", "inflammatory response", "neutrophil chemotaxis", "phagosome", and "platelet activation". Six hub genes and 12 common differentially expressed OSRGs were identified. A total of 168 miRNAs, 41 TFs, and 21 therapeutic drugs were predicted targeting these OSRGs. Lastly, the expression trends of Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 were confirmed in the external dataset and HR model. (4) Conclusions: Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 may be involved in the oxidative stress mechanism of MIRI, and the intervention of these genes may be a potential therapeutic strategy.

摘要

(1) 背景:氧化应激相关基因(OSRGs)在心肌缺血再灌注损伤(MIRI)中的分子机制尚未完全阐明。(2) 方法:对MIRI相关数据集GSE160516和GSE61592进行差异表达分析、富集分析和蛋白质-蛋白质相互作用(PPI)分析,以寻找关键途径和枢纽基因。OSRGs从分子特征数据库(MSigDB)中获取。基于其原始表达数据研究它们的表达模式和时间变化。使用相应的在线数据库预测靶向常见差异表达OSRGs的微小RNA(miRNAs)、转录因子(TFs)和治疗药物。在外部数据集GSE4105和H9C2细胞缺氧复氧(HR)模型中进一步验证这些鉴定出的OSRGs。(3) 结果:共鉴定出134个MIRI差异表达基因(DEGs),这些基因富集于“免疫反应”“炎症反应”“中性粒细胞趋化”“吞噬体”和“血小板活化”途径。鉴定出6个枢纽基因和12个常见差异表达OSRGs。共预测出168个miRNAs、41个TFs和21种靶向这些OSRGs的治疗药物。最后,在外部数据集和HR模型中证实了Aif1、Apoe、Arg1、Col1a1、Gpx7和Hmox1的表达趋势。(4) 结论:Aif1、Apoe、Arg1、Col1a1、Gpx7和Hmox1可能参与MIRI的氧化应激机制,对这些基因的干预可能是一种潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c294/9961140/5e45844b890f/jcdd-10-00079-g001.jpg

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