缺血性脑卒中关键基因的筛选及治疗药物的预测

Screening of key genes and prediction of therapeutic agents forischemic stroke based on transcriptome sequencing andbioinformatics methods

运用生物信息学方法初步筛选缺血性脑卒中(ischemic stroke,IS)相关的差异表达基因(differentially expressed genes,DEGs)和关键基因(hub genes),进而预测潜在的IS治疗药物。对正常组和双侧颈内动脉闭塞(bilateral internal carotid artery occlusion,BICAO)组的大鼠皮层进行转录组测序(RNA-sequencing,RNA-Seq),对筛选得到的DEGs进行GO和KEGG富集分析,并构建DEGs的蛋白互作网络,获得关键基因,根据关键基因预测IS相关药物。本研究共得到197个显著DEGs,这些基因主要参与代谢、神经活性配体-受体相互作用、补体和凝血级联反应、类固醇激素生物合成等途径。DEGs间有着紧密的相互关系,相互关系最为密切的基因中,ORM1、SERPINA1、GC都参加炎症、氧化应激和凋亡过程,是IS发病过程的关键基因。因此,炎症、氧化应激和凋亡在IS的发生发展中起重要作用,针对IS的关键基因如ORM1、SERPINA1、GC进行药物治疗有潜在的临床意义。

In this study,bioinformatics methods were used to preliminarily screen ischemic stroke(IS)-related differentially expressed genes(DEGs)and hub genes,and then predict potential IS therapeutics.DEGs were screened after transcriptome sequencing(RNA-Seq)in the cortex of the normal group and the bilateral internal carotid artery occlusion(BICAO)group.GO and KEGG enrichment analysis of DEGs were performed and protein interaction networks of DEGs were constructed,and key genes were obtained.Finally,IS related drugs were predicted according to the key genes.A total of 197 significant DEGs were obtained in this study,and enrichment analysis showed that these genes were mainly involved in metabolism,neuroactive ligandreceptor interactions,complement/coagulation cascade and biosynthesis of steroid hormones.DEGs have a close interrelationship,and among the genes most closely related,ORM1,SERPINA1 and GC all participate in the process of inflammation,oxidative stress and apoptosis,which are the key genes in the pathogenesis of IS.Therefore,inflammation,oxidative stress and apoptosis may be closely related to the occurrence and development of IS.It has potential clinical significance for drug treatment targeting hub genes such as ORM1,SERPINA1,and GC.