脑缺血和再灌注损伤的遗传转录谱仍然难以捉摸。为了解决这个问题,我们使用了一种综合分析方法,包括差异表达基因(DEG)分析,加权基因共表达网络分析(WGCNA),以及途径和生物过程分析,以分析大脑中动脉阻塞(MCAO)后9只小鼠和5只大鼠的微阵列研究数据以及基因表达综合(GEO)中的6个原代细胞转录数据集。(1)我们确定了58个增加超过2倍的上调DEG,和adj.在小鼠数据集中p<0.05。其中,Atf3,Timp1,Cd14,Lgals3,Hmox1,Ccl2,Emp1,Ch25h,Hspb1,Adamts1,Cd44,Icam1,Anxa2,Rgs1和Vim在小鼠和大鼠数据集中均显示出显着增加。(2)缺血处理和再灌注时间是影响基因谱改变的主要混杂因素,而采样部位和缺血时间均无。(3)WGCNA确定了再灌注时间无关和炎症相关模块以及再灌注时间相关和血栓-炎症相关模块。星形胶质细胞和小胶质细胞是这两个模块中基因变化的主要贡献者。(4)鉴定了44个模块核心hub基因。我们验证了未报告的卒中相关核心中心或人类卒中相关核心中心的表达。Zfp36mRNA在永久性MCAO中上调;Rhoj,Nfkbiz,Ms4a6d,Serpina3n,Adamts-1,Lgals3和Spp1mRNA在瞬时MCAO和永久性MCAO中均上调;NFKBIZ,ZFP3636和MAFF蛋白,未报告的核心中心与炎症的负调节有关,在永久性MCAO中上调,但不是在短暂的MCAO。总的来说,这些结果扩大了我们对脑缺血和再灌注的遗传特征的认识,强调炎症不平衡在脑缺血中的关键作用。
The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed gene (DEG) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological process analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO) and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). (1) We identified 58 upregulated DEGs with more than 2-fold increase, and adj. p < 0.05 in mouse datasets. Among them, Atf3, Timp1, Cd14, Lgals3, Hmox1, Ccl2, Emp1, Ch25h, Hspb1, Adamts1, Cd44, Icam1, Anxa2, Rgs1, and Vim showed significant increases in both mouse and rat datasets. (2) Ischemic treatment and reperfusion time were the main confounding factors in gene profile changes, while sampling site and ischemic time were not. (3) WGCNA identified a reperfusion-time irrelevant and inflammation-related module and a reperfusion-time relevant and thrombo-inflammation related module. Astrocytes and microglia were the main contributors of the gene changes in these two modules. (4) Forty-four module core hub genes were identified. We validated the expression of unreported stroke-associated core hubs or human stroke-associated core hubs. Zfp36 mRNA was upregulated in permanent MCAO; Rhoj, Nfkbiz, Ms4a6d, Serpina3n, Adamts-1, Lgals3, and Spp1 mRNAs were upregulated in both transient MCAO and permanent MCAO; and NFKBIZ, ZFP3636, and MAFF proteins, unreported core hubs implicated in negative regulation of inflammation, were upregulated in permanent MCAO, but not in transient MCAO. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.