驻春胶囊通过TNFRSF1A调节NK细胞活性治疗肾阳虚型骨质疏松症  

Study on Zhuchun Capsules in Treating Kidney-Yang Deficiency Osteoporosis Through TNFRSF1A Regulation of NK Cell Activity

作　　者：耿端 曹向阳 李俊辉 张迪 GENG Duan;CAO Xiangyang;LI Junhui;ZHANG Di(Luoyang Orthopedic-Traumatological Hospital of Henan Province,Henan Provincial Orthopedic Hospital,Zhengzhou,Henan,China,450016)

机构地区：[1]河南省洛阳正骨医院,河南省骨科医院,河南郑州450016

出　　处：《河南中医》2024年第11期1707-1717,共11页Henan Traditional Chinese Medicine

基　　金：河南省重大科技专项项目(221100310200)。

摘　　要：目的:运用网络药理学和生物信息学技术探讨驻春胶囊治疗肾阳虚型骨质疏松症的作用机制。方法:使用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选驻春胶囊组方中药的活性成分,并使用TCMSP和Drugbank数据库检索有效成分相关靶点。在GeneCards数据库、药物靶标数据库(therapeutic target database,TTD)和人类在线孟德尔遗传数据库(online mendelian inheritance in man,OMIM)中检索骨质疏松症致病靶点;在GEO数据库中筛选肾阳虚型骨质疏松症患者与正常人之间的差异表达基因;将两者取交集,得到肾阳虚型骨质疏松症致病靶点。将活性成分相关靶点与肾阳虚型骨质疏松症致病靶点取交集,得到驻春胶囊治疗肾阳虚型骨质疏松症的潜在靶点。利用Cytoscape 3.9.1软件构建“药物-活性成分-潜在靶点”网络。利用R软件对潜在靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopediaof genes and genome,KEGG)信号通路富集分析。采用STRING数据库进行聚类关联分析,并通过CytoNCA分析筛选驻春胶囊治疗肾阳虚型骨质疏松症的关键靶基因。采用AutodockVina软件对活性成分和关键靶基因进行分子对接验证;采用CIBERSORT进行免疫细胞浸润分析。结果:本研究共筛选得到183个活性成分、2732个活性成分相关靶点、897个肾阳虚型骨质疏松症的疾病靶点。将活性成分相关靶点与疾病靶点取交集,得到34个驻春胶囊治疗肾阳虚型骨质疏松症的潜在靶点。“药物-活性成分-潜在靶点”网络分析得到木犀草素、8-异戊烯-山柰酚(8-isopentenyl-kaempferol)、黄豆黄素(glycitein)、柚皮素(naringenin)、槲皮素(quercetin)等有效活性成分和SIRT1、CDKN1B、TNFRSF1A等潜在靶基因。GO和KEGG通路富集分析显示,主要靶点富集在多个细胞组分、生物过程及信号通路上。PPIObjective:To explore the mechanism of Zhuchun Capsules in treating kidney-yang deficiency osteoporosis using network pharmacology and bioinformatics techniques.Methods:The active components of Zhuchun Capsules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Targets related to the active components were identified from the TCMSP and DrugBank databases.Osteoporosis-related targets were retrieved from the GeneCards,Therapeutic Target Database(TTD),and Online Mendelian Inheritance in Man(OMIM)database,and differentially expressed genes were identified in kidney-yang deficiency osteoporosis patients from the GEO database.The intersection of active compound-related targets and disease targets was analyzed to identify potential targets for Zhuchun Capsules in treating kidney-yang deficiency osteoporosis.Cytoscape 3.9.1 software was used to construct a"drug-active component-potential target"network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using R software.STRING and CytoNCA analyses were performed to identify key genes involved in the treatment.Molecular docking was verified using Autodock Vina,and immune infiltration analysis was conducted using CIBERSORT.Results:A total of 183 active components,2732 related targets and 897 disease-related targets were identified.The intersection revealed 34 potential targets for Zhuchun Capsules in treating kidney-yang deficiency osteoporosis.The"drug-active component-potential target"network analysis identified effective active components such as luteolin,8-isopentenyl-kaempferol,glycitein,naringenin,and quercetin,as well as potential target genes including SIRT1,CDKN1B,and TNFRSF1A,etc.GO and KEGG pathway enrichment analysis revealed that the main targets are enriched in various cellular components,biological processes,and signaling pathways.PPI network analysis identified SIRT1,CDKN1B,and TNFRSF1A as the key target genes for Zhuchun Capsules in treating

关 键 词：驻春胶囊 骨质疏松症 肾阳虚证 免疫浸润 网络药理学 生物信息学 TNFRSF1A NK细胞 

分 类 号：R285.5[医药卫生—中药学]