摘要
目的利用生物信息学方法筛选湿性年龄相关性黄斑变性(wet age-related macular degeneration,w AMD)的氧化应激相关差异表达基因及靶向中药,以期为wAMD的预防和治疗提供新思路。方法从GEO数据库中筛选数据集,利用R软件limma包筛选差异基因,从Genecard数据库筛选氧化应激差异基因,并利用韦恩图得到共有基因。应用Metascape对氧化应激差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析,并通过String数据库构建蛋白质相互作用(protein-protein interaction,PPI)网络,再通过Cytoscape软件筛选出wAMD中氧化应激的关键(Hub)基因。采用GSE103060数据集验证Hub基因的差异表达。利用Coremine Medical预测靶向中药。结果经筛选共得到差异表达基因1874个,其中上调基因747个,下调基因1127个。KEGG富集分析表明,差异表达基因主要富集于细胞外基质受体相互作用、黏附斑激酶通路、河马(Hippo)信号通路、晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路、钙信号通路和磷脂酰肌醇-3-羟激酶(phosphatidylinositol-3-hydroxykinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路。通过PPI网络筛选得到与w AMD氧化应激密切相关的8个Hub基因,分别为IL6、EGFR、HIF1A、APOE、FN1、PPARG、EDN1和NGF。最后在GSE103060数据集中验证了以上Hub基因的显著差异表达。利用Coremine Medical预测人参、黄芪、枸杞子、丹参、银杏叶等可作为预防或治疗wAMD的靶向中药。结论通过对w AMD芯片的挖掘和生物信息分析,差异基因主要富集于氧化应激的相关通路与wAMD的氧化应激相关基因引起的。防治wAMD的首选中药为人参、黄芪、枸杞子、丹参和银杏叶等26种。这将对理解和探索wAMD的中医药防治策略有重要意义。
Objective Using bioinformatics methods to screen differential expression genes related to oxidative stress in wet agerelated macular degeneration(wAMD)and to identify targeted traditional Chinese medicine strategies,in order to provide new insights into the prevention and treatment of wAMD.Methods Datasets were selected from the GEO database,and differential genes were screened using the limma package in R software.Differential oxidative stress genes were selected from the Genecard database,and common genes were obtained using a Venn diagram.Metascape was used for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis of differential oxidative stress genes.A protein-protein interaction(PPI)network was constructed through the String database,and hub genes related to oxidative stress in wAMD were screened using Cytoscape software.The differential expression of hub genes was validated using the GSE103060 dataset.Coremine Medical was used to predict targeted traditional Chinese medicines.Results After screening,a total of 1874 differentially expressed genes(DEGs)were identified,including 747 upregulated genes and 1127 downregulated genes.KEGG enrichment analysis indicated that DEGs were mainly enriched in extracellular matrix-receptor interactions,focal adhesion kinase pathways,the Hippo signaling pathway,the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway,calcium signaling pathways,and phosphatidylinositol-3-hydroxykinase/protein kinase B(PI3K/Akt)signaling pathways.Eight Hub genes closely related to oxidative stress in wAMD were selected through the PPI network:IL6,EGFR,HIF1A,APOE,FN1,PPARG,EDN1,and NGF.The significant differential expression of these Hub genes was validated in the GSE103060 dataset.Coremine Medical predicted that Renshen(Ginseng Radix et Rhizoma),Huangqi(Astragali Radix),Goqizi(Lycii Fructus),Danshen(Salviae Miltiorrhizae Radix et Rhizoma),Yinxingye(Ginkgo Folium),and other Chinese medicines could be used as targeted preve
作者
崔高畅
Amy Yi Hsan Saik
张新慧
马玉玮
杨早
CUI Gaochang;Amy Yi Hsan Saik;ZHANG Xinhui;MA Yuwei;YANG Zao(M.Kandiah Faculty of Medicine and Health Sciences,Universiti Tunku Abdul Rahman,Selangor Kajang 43000,Malaysia;Faculty of Pharmacy,Ningxia Medical University,Yinchuan 750004,China)
出处
《中草药》
CAS
CSCD
北大核心
2024年第1期181-189,共9页
Chinese Traditional and Herbal Drugs
关键词
生物信息学
湿性年龄相关性黄斑变性
氧化应激
中药筛选
人参
黄芪
枸杞子
丹参
银杏叶
bioinformatics
wet age-related macular degeneration
oxidative stress
screening of traditional Chinese medicine
Ginseng Radix et Rhizoma
Astragali Radix
Lycii Fructus
Salviae Miltiorrhizae Radix et Rhizoma
Ginkgo Folium
