Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Jinan 250000, China.
Int J Med Sci. 2023 Sep 18;20(12):1562-1569. doi: 10.7150/ijms.87174. eCollection 2023.
: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model. : Gene expression profiling datasets (GSE72315 and GSE10654) and a microRNA (miRNA) expression profiling dataset (GSE72315) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and miRNAs (DEMiRs) were identified using online GEO2R or R before and after hepatic I/R injury in mice. Significant Gene Ontology (GO) terms were analyzed with the DAVID functional annotation tool. The DEMiR-miRNA target gene (miRTG) networks were constructed with miRTarBase, and the differentially expressed miRNAs and genes were analyzed with real-time quantitative polymerase chain reaction and immunofluorescence staining. : Through bioinformatic analysis, seven novel candidate miRNAs were identified that may regulate the expression of nine genes in hepatic I/R injury. Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes and were also significantly upregulated. : The decrease in miR-329-3p expression upregulated and expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.
肝缺血/再灌注（I/R）损伤在肝手术后很常见，尤其是在老年患者中。然而，对损伤机制的理解仍不完整。在这项研究中，我们在小鼠模型中探讨了肝 I/R 损伤的分子机制及其与年龄的关系。
从基因表达综合数据库（GEO）下载了基因表达谱数据集（GSE72315 和 GSE10654）和 miRNA 表达谱数据集（GSE72315）。使用在线 GEO2R 或 R 软件，在小鼠肝 I/R 损伤前后鉴定差异表达基因（DEGs）和 miRNA（DEMiRs）。使用 DAVID 功能注释工具分析显著的基因本体论（GO）术语。使用 miRTarBase 构建 DEMiR-miRNA 靶基因（miRTG）网络，并通过实时定量聚合酶链反应和免疫荧光染色分析差异表达的 miRNA 和基因。
通过生物信息学分析，鉴定出了七个可能调节肝 I/R 损伤中九个基因表达的新型候选 miRNA。在年轻（1 个月大）和年老（1 岁）小鼠的肝 I/R 损伤前后，mmu-miR-9-5p、mmu-miR-329-3p 和 mmu-miR-290a-5p 的表达均有显著差异。miR-329-3p 的差异表达最为显著，其预测靶基因 和 的表达也显著上调。
miR-329-3p 表达的降低以年龄独立的方式上调了小鼠肝 I/R 损伤中 和 的表达。这一发现有助于我们理解肝 I/R 损伤，并突出了未来治疗开发的新的分子靶标。
