基于生物信息分析焦亡在脑出血发病机制中的作用及临床意义

Analyze the Role and Clinical Significance of Pyroptosis in the Pathogenesis of Intracerebral Hemorrhage through Bioinformatics Analysis

目的:使用生物信息学对脑出血(intracerebral hemorrhage,ICH)患者的血肿周围组织及对照样本的基因芯片数据进行分析,确定与ICH后细胞焦亡相关的关键分子,进一步探讨ICH的病理机制及潜在的治疗靶点。方法:GEO数据库中选取4例ICH患者血肿周围组织和对侧相应部位(白质与灰质)正常脑组织样本中差异表达基因谱数据,对差异表达基因(differentially expressed genes,DRGs)和焦亡相关基因(pyroptosis-related genes,PRGs)进行合并分析,确定差异表达的焦亡相关基因(differentially expressed-PRGs,DE-PRGs)。对筛选出的DE-PRGs进行聚类,并进行GO、KEGG和蛋白相互作用网络分析。结果:与对照组织相比,在血肿周围组织中,共发现44个DE-PRGs。GO和KEGG分析表明,这44个DE-PRGs主要富含在细胞凋亡过程、炎症反应的正调控、核因子κB通路正调控、NOD-样受体信号通路及细胞焦亡过程中。对44个DE-PRGs进行蛋白质网络分析,筛选出10个关键基因:IL-1β、CXCL8、STAT3、TLR2、CASP1、ICAM1、IRF1、PTGS2、NLRP3和IL1RN;GO富集功能分析显示,这些关键基因在炎性反应、焦亡、信号通路等方面显著丰富。结论:本研究采用生物信息学分析发现了与ICH后焦亡相关的DE-PRGs 44个,进一步通过蛋白质网络分析筛选出10个关键基因,功能分析显示均与ICH后焦亡机制相关,可能是ICH的潜在治疗靶点。

Objective:To use bioinformatics to analyze the gene chip data of the tissue surrounding the hematoma and control samples from patients with intracerebral hemorrhage(ICH),identify key molecules related to cell pyroptosis after ICH,and further explore the pathological mechanisms and potential therapeutic targets of ICH.Methods:Differentially expressed gene profiles were selected from the GEO database for the tissue surrounding the hematoma of four ICH patients and the corresponding normal brain tissue samples(white and gray matter)from the contralateral side.The differentially expressed genes(DEGs)and pyroptosis-related genes(PRGs)were merged and analyzed to identify differentially expressed PRGs(DE-PRGs).GO,KEGG enrichment analyses,and protein-protein interaction(PPI)analyses were performed on the identified DE-PRGs.Results:Compared with control tissue,a total of 44 DE-PRGs were found in the tissue surrounding the hematoma.GO and KEGG analyses indicated that these 44 DE-PRGs were mainly enriched in processes such as apoptosis,positive regulation of inflammatory response,positive regulation of the NF-κB pathway,NOD-like receptor signaling pathway,and pyroptosis.PPI analysis of the 44 DE-PRGs identified 10 key genes:IL-1β,CXCL8,STAT3,TLR2,CASP1,ICAM1,IRF1,PTGS2,NLRP3,and IL1RN.GO enrichment functional analysis showed that these key genes were significantly enriched in inflammatory response,pyroptosis,and signaling pathways.Conclusion:This study identified 44 DE-PRGs related to pyroptosis after ICH through bioinformatics analysis and further screened out 10 key genes through PPI analysis.Functional analysis showed that all were related to the mechanism of pyroptosis after ICH and may be potential therapeutic targets for ICH.