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

doi:10.3969/j.issn.1673-5765.2025.09.011

中国卒中杂志 ›› 2025, Vol. 20 ›› Issue (9): 1157-1166.DOI: 10.3969/j.issn.1673-5765.2025.09.011

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

贾瑞琪，翟华筝，张晨，汪敬业

合肥 230022 安徽医科大学第一附属医院神经内科

收稿日期:2025-02-20 修回日期:2025-06-20 接受日期:2025-06-27 出版日期:2025-09-20 发布日期:2025-09-20
通讯作者: 汪敬业 jyewang@163.com
基金资助:
安徽省卫生健康科研项目（AHWJ2024Aa20030）
安徽省转化医学研究院科研基金项目重点项目（2023zhyx-B04)
安徽医科大学校科研基金（2022xkj142)

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

JIA Ruiqi, ZHAI Huazheng, ZHANG Chen, WANG Jingye

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

Received:2025-02-20 Revised:2025-06-20 Accepted:2025-06-27 Online:2025-09-20 Published:2025-09-20
Contact: WANG Jingye, E-mail: jyewang@163.com

摘要/Abstract

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。

文章导读： 本研究通过RNA测序技术分析大鼠全脑缺血再灌注损伤后海马CA1区基因表达变化，发现与假手术组相比，模型组的基因差异表达呈现双相变化，有多个共同基因和通路参与缺血再灌注过程，这可能为神经保护治疗提供潜在的作用靶点。

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

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

中图分类号:

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.

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.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.chinastroke.org.cn/CN/10.3969/j.issn.1673-5765.2025.09.011

https://www.chinastroke.org.cn/CN/Y2025/V20/I9/1157

参考文献

[1] WANG W Z，LIU L X，CHEN C，et al. Protective effects of dopamine D2/D3 receptor agonist piribedil on learning and memory of rats exposed to global cerebral ischemia-reperfusion[J/OL]. Neurosci Lett，2018，684：181-186[2025-05-10]. https://doi.org/10.1016/j.neulet.2018.08.011.
[2] SUN W，CHEN Y T，ZHANG Y J，et al. A modified four vessel occlusion model of global cerebral ischemia in rats[J/OL]. J Neurosci Methods，2021，352：109090[2025-05-15]. https://doi.org/10.1016/j.jneumeth.2021.109090.
[3] SCHMIDT-KASTNER R. Genomic approach to selective vulnerability of the hippocampus in brain ischemia-hypoxia[J/OL]. Neuroscience，2015，309：259-279[2025-05-15]. https://doi.org/10.1016/j.neuroscience.2015.08.034.
[4] SCHMIDT-KASTNER R，FREUND T F. Selective vulnerability of the hippocampus in brain ischemia[J]. Neuroscience，1991，40（3）：599-636.
[5] BARTSCH T，DÖHRING J，REUTER S，et al. Selective neuronal vulnerability of human hippocampal CA1 neurons：lesion evolution，temporal course，and pattern of hippocampal damage in diffusion-weighted MR imaging[J]. J Cereb Blood Flow Metab，2015，35（11）：1836-1845.
[6] WANG C M，LIU M H，PAN Y Y，et al. Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model[J]. Oncotarget，2017，8（43）：74607-74622.
[7] DERGUNOVA L V，FILIPPENKOV I B，STAVCHANSKY V V，et al. Genome-wide transcriptome analysis using RNA-seq reveals a large number of differentially expressed genes in a transient MCAO rat model[J/OL]. BMC Genomics，2018，19（1）：655[2025-05-15]. https://doi.org/10.1186/s12864-018-5039-5.
[8] SHI J L，CHEN X，LI H Y，et al. Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury[J/OL]. Sci Rep，2017，7（1）：5800[2025-05-15]. https://doi.org/10.1038/s41598-017-05342-9.
[9] MOVAHED M，BROCKIE S，HONG J，et al. Transcriptomic hallmarks of ischemia-reperfusion injury[J/OL]. Cells，2021，10（7）：1838[2025-05-20]. https://doi.org/10.3390/cells10071838.
[10] HORN M，SCHLOTE W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia[J]. Acta Neuropathol，1992，85（1）：79-87.
[11] ZHANG Y，CHEN Q B，CHEN D S，et al. SerpinA3N attenuates ischemic stroke injury by reducing apoptosis and neuroinflammation[J]. CNS Neurosci Ther，2021，28（4）：566-579.
[12] LI F S，ZHANG Y M，LI R Q，et al. Neuronal SerpinA3N is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke[J]. J Cereb Blood Flow Metab，2023，43（2）：241-257.
[13] MUHAMMAD I F，BORNÉ Y，MELANDER O，et al. FADD（fas-associated protein with death domain），caspase-3，and caspase-8 and incidence of ischemic stroke[J]. Stroke，2018，49（9）：2224-2226.
[14] KAWA H，AHMED Z，MAJID A，et al. Inhibition of matrix metalloproteinases to reduce blood brain barrier disruption and haemorrhagic transformation in ischaemic stroke：go broad or go narrow？[J/OL]. Neuropharmacology，2025，262：110192[2025-05-11]. https://doi.org/10.1016/j.neuropharm.2024.110192.
[15] CHELLUBOINA B，KLOPFENSTEIN J D，PINSON D M，et al. Matrix metalloproteinase-12 induces blood-brain barrier damage after focal cerebral ischemia[J]. Stroke，2015，46（12）：3523-3531.
[16] CHALLA S R，NALAMOLU K R，FORNAL C A，et al. Therapeutic efficacy of matrix metalloproteinase-12 suppression on neurological recovery after ischemic stroke：optimal treatment timing and duration[J/OL]. Front Neurosci，2022，16：1012812[2025-05-14]. https://doi.org/10.3389/fnins.2022.1012812.
[17] WILLIAMS R S. Heat shock proteins and ischemic injury to the myocardium[J]. Circulation，1997，96（12）：4138-4140.
[18] KIM J Y，KIM J W，YENARI M A. Heat shock protein signaling in brain ischemia and injury[J/OL]. Neurosci Lett，2020，715：134642[2025-05-10]. https://doi.org/10.1016/j.neulet.2019.134642.
[19] BAI J L，LYDEN P D. Revisiting cerebral postischemic reperfusion injury：new insights in understanding reperfusion failure，hemorrhage，and edema[J]. Int J Stroke，2015，10（2）：143-152.
[20] CANDELARIO-JALIL E，DIJKHUIZEN R M，MAGNUS T. Neuroinflammation，stroke，blood-brain barrier dysfunction，and imaging modalities[J]. Stroke，2022，53（5）：1473-1486.

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

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	何丹丹, 李俭, 王春娟, 李姝雅. 我国急性缺血性卒中脑细胞保护剂基础实验与临床研究的挑战与突破[J]. 中国卒中杂志, 2026, 21(5): 517-524.
[2]	程希玥, 赵璟妍, 王春娟. 依达拉奉右莰醇在急性缺血性卒中脑细胞保护中的研究进展[J]. 中国卒中杂志, 2026, 21(5): 526-532.
[3]	杨千千, 张眉扬, 陆瑶, 周东杨, 王正一蕾, 单舒乙, 刘晨辉, 王伊龙, 管玲. 米诺环素在急性缺血性卒中中的抗神经炎症与脑细胞保护研究进展：从机制到临床证据[J]. 中国卒中杂志, 2026, 21(5): 533-542.
[4]	何丹丹, 李姝雅. 基于STAIR原则的PSD-95靶向脑细胞保护剂在急性缺血性卒中中的研究进展[J]. 中国卒中杂志, 2026, 21(5): 543-552.
[5]	陈壮壮, 徐柳, 王楠星, 张眉扬, 姬若冰, 杨沫, 刘向荣, 王伊龙. 经颅骨骨髓途径递送脑细胞保护剂的研究与展望[J]. 中国卒中杂志, 2026, 21(5): 553-560.
[6]	陈玮琪, 江凌玲, 何菂, 陈彦博, 张枘南, 刘欣如, 刘文竹, 郭蕾, 王玲, 王伊龙. 干细胞衍生物：突破活细胞治疗局限的多靶点脑细胞保护生物制品[J]. 中国卒中杂志, 2026, 21(5): 561-569.
[7]	常曹文静, 许淑红, 李俭, 李姝雅. 载脂蛋白E基因与缺血性卒中后脑损伤关系的研究进展[J]. 中国卒中杂志, 2026, 21(5): 570-576.
[8]	李汶逸, 姜季委, 任琦玮, 王琳琳, 赵敏, 徐俊. 载脂蛋白E基因多态性与卒中后认知功能变化的相关性研究[J]. 中国卒中杂志, 2026, 21(5): 577-584.
[9]	张惠琴, 杜丽娟, 张萌, 吕一飞, 何文, 张巍. 经食管超声心动图在心源性卒中病因筛查中的价值[J]. 中国卒中杂志, 2026, 21(5): 585-592.
[10]	刘言祥, 李颖, 常静玲. 卒中后急性期伴认知障碍的脑电图微状态研究[J]. 中国卒中杂志, 2026, 21(5): 593-602.
[11]	王露妍, 周梦圆, 郭毅佳, 潘岳松, 王伊龙. 稳态负荷评分与COVID-19人群脑小血管病影像学进展的关联：基于社区人群的队列研究[J]. 中国卒中杂志, 2026, 21(5): 603-611.
[12]	彭艳, 冯文战, 刘沁, 唐红梅, 刘祎, 高立, 汪思嘉, 白雪. 大鼠miR-664-1-5p靶向PTEN/Akt/Nrf2通路减轻缺氧/复氧PC12细胞氧化损伤的机制研究[J]. 中国卒中杂志, 2026, 21(5): 612-623.
[13]	中国康复医学会重症康复专业委员会呼吸重症学组, 中国医师协会康复医师分会重症康复学组, 北京康复医学会重症康复专业委员会. 神经重症患者呼吸功能重建中国专家共识[J]. 中国卒中杂志, 2026, 21(5): 624-649.
[14]	张效良, 刘岩. 表现为急性孤立性体位性头痛的小脑梗死1例报道[J]. 中国卒中杂志, 2026, 21(5): 650-656.
[15]	黄卫, 褚晓婷, 万秋萍, 虞慧婷, 杨晓明. 从监测到干预：卒中防控公共卫生实践路径的思考[J]. 中国卒中杂志, 2026, 21(4): 387-397.