高血压合并心力衰竭相关基因的筛选、分析及验证

Screening,bioinformatics analysis and validation of hypertension combined with heart failure-related genes

目的:筛选、分析高血压合并心力衰竭(心衰)的差异基因并通过实验验证。方法:从GEO数据库中搜索并下载与高血压合并心衰相关的mRNA芯片数据集GSE2116和GSE19210,使用R语言软件分析差异基因并筛选得到二者芯片共同的差异基因。通过Metascape对差异基因进行富集分析,运用STRING工具构建差异基因的蛋白互作网络,并使用Cytoscape分析其中的关键基因。最后构建高血压合并心衰的模型大鼠,并通过qRT-PCR检测关键基因在模型大鼠左心室组织的表达情况。结果:从芯片中筛选得到50个表达上调和32个表达下调的共同差异基因,功能分析显示其主要富集于炎症反应、氧化应激反应、PI3K/Akt信号通路和Toll样受体通路。构建蛋白互作网络并从中分析筛选得到10个关键的差异基因,qRT-PCR的结果表明除Lbp外其余9个关键基因的表达情况与芯片结果一致。结论:本实验应用生物信息学分析的方法筛选出高血压合并心衰相关的差异基因,并对其进行了功能分析和实验验证,为寻找与高血压合并心衰发生发展及治疗相关靶点的研究提供了新的思路。

Objective:To screen out and validate the co-differentially expressed genes(co-DEGs)related to hypertension combined with heart failure by bioinformatics analysis.Method:Two different gene expression profiles related to hypertension combined with heart failure of GSE2116 and GSE19210 were downloaded from Gene Expression Omnibus(GEO).The co-DEGs that up-regulated or down-regulated in both two gene expression profiles were analysed using R project.Metascape was used to enrichment analysis for the co-DEGs.The key DEGs were screen out from PPI network constructed by STRING.Hypertension combined with heart failure model rats were conducted and qRT-PCR was used to measure the mRNA expression level of the key DEGs.Result:After intersection,50 up-regulated and 32 down-regulated co-DEGs were screened out.The co-DEGs were mainly enriched in inflammatory response,response to reactive oxygen species,PI3 K-Akt signaling pathway and Toll-like receptor signaling pathway basing on enrichment analysis.10 key DEGs with high degrees in the protein-protein interaction network were screened out.qRT-PCR approved that the mRNA expression level of the key DEGs in addition to Lbp were consistent with the gene expression profiles.Conclusion:In this study,the DEGs associated with hypertension and heart failure were screened by bioinformatics analysis,and their function analysis and experimental verification were carried out,which provided a new idea for the research on the development and treatment of hypertension and heart failure.