本文主要对大鼠、小鼠盲肠结扎穿刺术(CLP)脓毒血症模型进行分析, 从模式动物角度发现潜在的脓毒血症相关基因, 为脓毒血症诊疗提供理论依据。从NCBI-Gene Expression Omnibus数据库下载原始微阵列数据集, 然后纳入盲肠结扎穿刺术脓毒血症及假手术组模型数据。运用生物信息学方法将数据标准化处理后, 筛选差异基因进行富集分析和通路分析, 并构建蛋白质相互作用关系网络, 筛选出具有重要生理调节功能的核心蛋白质和关键候选基因。通过大鼠盲肠穿刺脓毒血症诱导后肝组织的差异基因表达芯片筛选, 共获得350个能上调1.5倍及以上的差异基因, 1 337个能下调2倍及以上的差异基因; 通过小鼠盲肠穿刺脓毒血症诱导后肝组织的差异基因表达芯片筛选, 获得3 532个上调1.5倍及以上的差异基因, 4 020个下调1.5倍及以上的差异基因; 对上述芯片结果的差异基因取交集, 得到29个共同上调表达1.5倍以上的差异基因和84个共同下调表达1.5倍以上的差异基因。利用String数据库对上述基因进行蛋白质-蛋白质的相互作用(PPI)网络分析, 并利用David数据库从生物过程(BP)、分子功能(MF)、细胞组分(CC)和KEGG(Kyoto encyclopedia of genes and genomes)通路4个角度进行基因功能分析, 发现共有10条通路与脓毒血症肝组织关系密切, 其中最主要的通路为丝裂原活化蛋白激酶(MAPK)通路, 其次, 缺氧诱导因子1(HIF-1)、叉形头转录因子的O亚型(FoxO)、乙型肝炎、血小板激活及胆汁分泌等通路调控也与脓毒血症相关。本研究为进一步探讨脓毒血症相关病理生理机制及诊疗方法提供了理论基础。

The sepsis models of cecal ligation and puncture(CLP) in rats and mice were analyzed, and potential sepsis-related genes were found from the perspective of model animals, providing a theoretical basis for diagnosis and treatment of sepsis. After downloading the original microarray data set from the NCBI-Gene Expression Omnibus database (NCBI-GEO), cecal ligation puncture sepsis model and sham operation groups were included. Bioinformatics methods are used to screen differential genes after standardization of data. Then we performed enrichment analysis and pathway analysis, constructed a protein interaction network to screen core proteins and key candidate genes with important physiological regulatory functions. Through the differential gene expression chip screening of liver tissues after cecal puncture in rats, we obtained 350 differential genes that were up-regulated 1.5 times and more, and 1 337 differential genes that were down-regulated 2 times and more. Screening of differential gene expression chips of liver tissues after sepsis induction in mice yielded 3 532 differential genes that were up-regulated 1.5 times or more, and 4 020 differential genes that were down-regulated 1.5 times or more. According to the overlap of the differential genes from the above chip results, 29 differentially expressed genes were up-regulated more than 1.5 times, and 84 differentially expressed genes were down-regulated. Besides performing a protein-protein interaction (PPI) network, biological processes (BP), molecular functions (MF), cellular components (CC) and KEGG(Kyoto encyclopedia of genes and genomes) pathway analysis of gene function on the above genes in the David database, we found that a total of 10 pathways are closely related to sepsis liver tissue. The most important pathway is the MAPK pathway, followed by HIF-1 (hypoxia inducible factor 1), FoxO (forkhead box, sub-group O), hepatitis B, platelet activation and bile regulation of secretory pathways. This provides a theoretical basis for our further research on the pathophysiology and diagnosis and treatment of sepsis.