Study on Dynamic Changes of Gene Expression in the Hippocampus CA1 Region after Global Cerebral Ischemia-Reperfusion Injury in Rats

doi:10.3969/j.issn.1673-5765.2025.09.011

Abstract

Abstract: Objective After global cerebral ischemia-reperfusion injury, neuronal death in the hippocampal CA1 region is the most prominent, yet the underlying mechanisms remain unclear. This study analyzes the genomic changes in the hippocampal CA1 region after global cerebral ischemia-reperfusion injury in rats, aiming to identify potential interventional targets.
Methods Sprague-Dawley rats were randomly divided into the sham-operated group and the model group. A rat model of global cerebral ischemia-reperfusion injury was established using the four-vessel occlusion method. RNA sequencing was performed in the hippocampal CA1 region at five time points (6, 12, 24, 48, 72 hours) after ischemia-reperfusion in the sham-operated group and the model group. The sequencing results were analyzed by comparative analysis, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.
Results Cluster analysis revealed that there were significant differences in gene expression between the sham-operated group and the model groups at different time points after global cerebral ischemia-reperfusion injury, with a greater number of up-regulated genes. Enrichment analysis showed that the co-differentially expressed genes were primarily enriched in pathways such as inflammatory response, positive regulation of cell migration, negative regulation of cell differentiation, regulation of intercellular adhesion, and regulation of apoptotic signaling pathway. Both the number of differentially expressed genes and the enriched GO terms and KEGG pathways exhibited two peaks at 12 hours and 48 hours, suggesting that the gene expression after acute global cerebral ischemia-reperfusion injury showed biphasic changes.
Conclusions Multiple common genes and pathways are involved in the process of ischemia-reperfusion injury after global cerebral ischemia-reperfusion injury. These genes are primarily involved in inflammatory-immune regulation and cell death mechanisms, with their expression exhibiting biphasic changes. These findings suggest the involvement of complex pathways and regulatory mechanisms after ischemia-reperfusion.

Key words: Global cerebral ischemia-reperfusion injury; RNA sequencing; Differentially expressed gene; Hippocampus

摘要： 目的全脑缺血再灌注损伤后海马CA1区神经元死亡最为显著，但其原因尚不明确。本研究分析大鼠全脑缺血再灌注损伤后海马CA1区的基因组变化，寻找可能的干预靶点。
方法将Sprague-Dawley大鼠随机分为假手术组和模型组。采用四血管法制作大鼠全脑缺血再灌注损伤模型。假手术组及模型组大鼠在全脑缺血再灌注后的5个时间点（6、12、24、48、72 h）取海马CA1区脑组织进行RNA测序。测序结果采用对比分析、基因本体论（gene ontology，GO）富集分析，以及京都基因和基因组数据库（Kyoto encyclopedia of genes and genomes，KEGG）通路分析。
结果聚类分析显示，假手术组与全脑缺血再灌注损伤后不同时间点模型组的基因表达差异显著，上调基因数目较多。富集分析显示，共同差异表达基因主要富集于炎症反应、细胞迁移的正向调控、细胞分化的负调控、细胞间黏附的调控，以及凋亡信号通路的调控等途径。差异表达基因数目及富集到GO术语和KEGG通路数量有两个高峰，即在12 h和48 h，提示急性全脑缺血再灌注损伤后的基因表达呈现双相变化。
结论全脑缺血再灌注损伤后有多个共同基因和通路参与缺血再灌注损伤过程，主要涉及炎症免疫反应及细胞死亡相关基因，其表达呈现双相变化，提示缺血再灌注后存在复杂的通路和调控机制。

关键词: 全脑缺血再灌注损伤; 核糖核酸测序; 差异表达基因; 海马区

CLC Number:

JIA Ruiqi, ZHAI Huazheng, ZHANG Chen, WANG Jingye. Study on Dynamic Changes of Gene Expression in the Hippocampus CA1 Region after Global Cerebral Ischemia-Reperfusion Injury in Rats[J]. Chinese Journal of Stroke, 2025, 20(9): 1157-1166.

贾瑞琪, 翟华筝, 张晨, 汪敬业. 大鼠全脑缺血再灌注损伤后海马CA1区基因表达动态变化研究[J]. 中国卒中杂志, 2025, 20(9): 1157-1166.

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