Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model.
Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model.
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大鼠MCAO模型脑缺血再灌注损伤的整体基因表达谱
DOI：
10.18632/oncotarget.20253
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发表时间：
2017-09-26
期刊：
影响因子：
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通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Wang C;Liu M;Pan Y;Bai B;Chen J
众所周知，脑缺血损伤后的再灌注会引起继发性损伤，并伴有结构和功能损伤。然而，目前尚不清楚脑缺血再灌注损伤（IRI）中全局基因如何变化。本研究使用 RNA 测序策略研究了短暂性脑 IRI 后 Wistar 大鼠海马体的整体基因表达。结果显示，再灌注后24小时，156个基因上调≥2倍，26个基因下调≥2倍。选择15个差异表达基因来确认RNA测序结果。基因表达水平是动态的，每个基因的峰值表达水平出现在再灌注后的不同时间点。基因本体论（GO）分析将差异表达基因分类为主要涉及炎症、应激和免疫反应、糖代谢、促凋亡、抗凋亡和生物过程。 KEGG通路分析表明IRI激活不同的信号通路，包括粘着斑、肌动蛋白细胞骨架的调节、细胞因子-细胞因子受体相互作用、MAPK信号传导和Jak-STAT信号传导。本研究使用大脑中动脉闭塞 (MCAO) 模型描述了 Wistar 大鼠海马体的整体基因表达谱。这些发现为IRI的分子发病机制和未来预防和治疗IRI的潜在药物靶点提供了新的见解。
It is well-established that reperfusion following cerebral ischemic injury gives rise to secondary injury accompanied by structural and functional damage. However, it remains unclear how global genes changes in cerebral ischemia-reperfusion injury (IRI). This study investigated global gene expression in the hippocampi of Wistar rats following transient cerebral IRI using an RNA-sequencing strategy. The results revealed ≥2-fold up-regulation of 156 genes and ≥2-fold down-regulation of 26 genes at 24 h post-reperfusion. Fifteen differentially expressed genes were selected to confirm the RNA-sequencing results. Gene expression levels were dynamic, with the peak expression level of each gene occurring at different time points post-reperfusion. Gene Ontology (GO) analysis classified the differentially expressed genes as mainly involved in inflammation, stress and immune response, glucose metabolism, proapoptosis, antiapoptosis, and biological processes. KEGG pathway analysis suggested that IRI activated different signaling pathways, including focal adhesion, regulation of actin cytoskeleton, cytokine-cytokine receptor interaction, MAPK signaling, and Jak-STAT signaling. This study describes global gene expression profiles in the hippocampi of Wistar rats using the middle cerebral artery occlusion (MCAO) model. These findings provide new insights into the molecular pathogenesis of IRI and potential drug targets for the prevention and treatment of IRI in the future.