摘要
目的 利用生物信息学探究青娥丸治疗骨质疏松症(OP)的作用机制。方法 通过高通量基因表达数据库(CEO)检索OP相关芯片,利用R语言分析技术得到差异表达基因。借助GeneCards、DisGeNET、OMIM、MalaCards、PharmGKB数据库对OP已知靶基因进行检索与筛选,与差异表达基因去重取并集,对OP的疾病靶基因预测。运用中药系统药理学数据库与分析平台(TCMSP)及中药分子机制的生物信息学数据库(BATMAN-TCM)搜索青娥丸4味中药的有效成分并筛选和挖掘青娥丸有效成分的作用靶点,进一步构建药物与疾病映射靶基因,借助Cytoscape3.7.2软件构建“青娥丸药物-有效成分-靶点”网络图和蛋白质-蛋白质相互作用网络图(PPI网络图),得到青娥丸治疗OP的主要有效成分及关键靶基因。通过DAVID数据库对映射靶基因进行基因本体(GO)生物过程及京都基因与基因组百科全书(KEGG)通路富集分析。结果 检索GEO获得差异表达基因542个;检索疾病数据库获得与OP发生发展相关的已知疾病靶基因3576个,合并去重后共获得3811个已知疾病靶基因。在TCMSP和BATMAN-TCM中检索杜仲、补骨脂、核桃仁、大蒜4味中药的化学成分并通过蛋白质数据库(Unitprot)进行转换处理,得到青娥丸有效成分48个、作用靶点1757个,去重后为973个。将青娥丸有效成分对应的973个靶基因与3811个OP疾病靶基因交叉映射生成Venny图,获得映射靶基因433个。将433个映射靶基因导入Cytoscape3.7.2软件构建“青娥丸药物-有效成分-靶点”网络图和PPI网络图,分别得到β-谷甾醇、豆甾醇、异补骨脂素、槲皮素4种活性成分自由度较高的主要有效成分和27个关键靶基因。对433个映射靶基因采用DAVID数据库进行GO生物过程和KEGG信号通路分析,分别筛选出符合条件的20个生物过程和20条信号通路:青娥丸主要通过胰岛素(INS)、蛋白激敏B1(Akt1)、白细胞介素6(IL-6)、TP53、血�
Objective To explore the action mechanism of Qinge Pill for osteoporosis(OP)based on bioinformatics.Methods The differentially expressed genes(DEGs)were acquired by retrieving OP-related chips through high-throughput Gene Expression Omnibus(GEO)database by means of R language.The known target genes of OP were retrieved and screened out with GeneCards,DisGeNET,OMIM,MalaCards,PharmGKB databases,and the DEGs were subject to recombination elimination and union set to predict disease target genes of OP.Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM)were utilized to screen and mine primary effective components of Qinge Pill and targets of effective components,the drug and disease mapping target genes was further constructed,and the drug-effective components-target network and protein-protein interaction(PPI)network diagram were constructed using Cytoscape 3.7.2 software to obtain the effective components and key target genes of Qinge Pill.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on mapped target genes were implemented through David database.Results Totally 542 DEGs were acquired by high-throughput GEO database,3576 known disease target genes related to the occurrence and development of OP were searched from disease database,and 3811 known disease target genes were obtained after recombination elimination and union set.The chemical constituents of four traditional Chinese medicines(Eucommia,Psoralea,walnut kernel,garlic)were searched in TCMSP and BATMAN-TCM and converted via Universal Protein Resource(UniProt).There were 48 active ingredients representing 1757 targets,at last,973 targets were found after deduplication.The 973 target genes corresponding to the active ingredients of Qinge Pill and 3811 OP-related target genes were cross-mapped to generate a Venny diagram,and 433 mapped target genes were obtained.The genes were i
作者
王浩
谭国庆
薛海鹏
徐展望
WANG Hao;TAN Guoqing;XUE Haipeng;XU Zhanwang(Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250035;Department of Spine and Orthopedics,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250035)
出处
《河北中医》
2022年第9期1543-1548,1584,共7页
Hebei Journal of Traditional Chinese Medicine
基金
国家自然科学基金委员会资助项目(编号:81473709)
2018年全国名老中医药专家传承工作室建设项目(国中医药人教函[2018]134号)。
