脑出血后脑损伤的基因表达谱改变及相关小分子药物预测

Gene expression profile of brain injury after intracerebral hemorrhage and prediction of related small molecule drugs

目的研究脑出血(ICH)后局部脑组织的基因表达谱改变,为ICH的治疗提供靶点;以及预测可能用于ICH治疗的小分子化合物。方法从GEO数据库中下载GSE24265数据集,其中包括4个血肿周围组织和7个对侧脑组织(4个对侧白质,3个对侧灰质)的芯片数据。对数据进行归一化后,以log2FC>1和P<0.05为标准,筛选差异基因;对差异基因进行GO和KEGG分析。为了明确差异基因之间的关系,构建PPI网络。用CMap分析可能用于ICH治疗的小分子化合物。结果经过分析共得到69个差异基因,其中28个为上调基因、41个为下调基因。GO分析显示,ICH相关的差异基因主要的生物学过程有白细胞迁移、炎症反应、细胞粘附和信号转导等。KEGG分析得到了与ICH最显著相关的信号通路,包括c AMP信号通路、白细胞跨内皮迁移、松弛素信号通路、细胞因子-细胞因子受体相互作用等。PPI网络显示关键的节点基因有IL-1β、MMP-9、ITGAM、CAV1、KIT。CMap分析得到了5种可能用于ICH治疗的小分子化合物。结论本研究获得了ICH后表达水平显著改变的基因,如PROCR、HSD11B1、CTNNAL1、RPS4Y1、EIF1AY、KDM5D等。通过分析这些基因参与的信号通路和蛋白互相作用网络中的关键节点,得到了5种ICH治疗的候选药物。

Objective To study the changes of gene expression profile in local brain tissue after intracerebral hemorrhage(ICH),so as to provide targets for the treatment of ICH and to predict small molecular compounds that might be used.Methods The GSE24265 data set was downloaded from the GEO database,including chip data of 4 perihematoma tissues and 7 contralateral brain tissues(4 contralateral white matter and 3 contralateral gray matter).After the data were normalized,the differential genes were screened according to log2FC>1 and P<0.05.The differential genes were analyzed by GO and KEGG.In order to clarify the relationship between different genes,PPI network was constructed.Small molecular compounds that may be used in ICH treatment were analyzed by CMap.Results A total of 69 differential genes were obtained,including28 up-regulated genes and 41 down-regulated genes.GO analysis showed that the main biological processes of ICH related differential genes were leukocyte migration,inflammatory response,cell adhesion and signal transduction.KEGG analysis obtained the most significant signal pathways related to ICH,including c AMP signal pathway,leukocyte cross endothelial migration,relaxin signal pathway,cytokine cytokine receptor interaction and so on.PPI network showed that the key node gene was IL-1β、MMP-9、ITGAM、CAV1、KIT.Five small molecular compounds that may be used in ICH treatment were obtained by CMAP analysis.Conclusions In this study,genes with significant changes in expression level after ICH were obtained,such as PROCR,HSD11B1,CTNNAL1,RPS4Y1,EIF1AY,KDM5D,etc.By analyzing the signal pathways involved in these genes and the key nodes in the protein interaction network,five candidate drugs for ICH treatment were obtained.