首页|基于网络药理学探讨真武汤治疗特发性膜性肾病的作用机制

基于网络药理学探讨真武汤治疗特发性膜性肾病的作用机制

Mechanism of action of Zhenwu decoction in treatment of idiopathic membranous nephropathy:A study based on network pharmacology

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目的:通过网络药理学及GEO数据库,探讨真武汤治疗特发性膜性肾病(IMN)的作用机制.方法:运用TCMSP检索真武汤有效活性成分及靶点,利用GeneCards等4个数据库获得IMN靶点,采用STRING数据库和Cytoscape软件构建药物-成分-靶点-疾病相互作用网络和蛋白质-蛋白质相互作用(PPI)核心靶点网络,并进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最后进行分子模拟对接,并基于GEO进行核心靶点基因差异表达分析及免疫细胞浸润分析验证.结果:真武汤治疗IMN的关键活性成份是豆甾醇、山柰酚、β-谷甾醇等,其中核心靶点为丝氨酸苏氨酸蛋白激酶-1(AKT1)、转录因子AP-1(JUN)、半胱氨酸天冬氨酸蛋白酶-3(CASP3)等,KEGG富集分析发现主要作用在流体剪切应力等117条信号通路;分子对接显示山柰酚、β-谷甾醇与前列腺素G/H合成酶-2(PTGS2)、CASP3、AKT1等靶点具有较强结合力;GSE115857数据集中AKT1、细胞间黏附分子-1(ICAM1)、CASP3为上调基因,JUN为下调基因,这些可能与未活化的CD4记忆性T细胞、未活化的自然杀伤细胞等免疫细胞有关.结论:真武汤通过多成份、多靶点、多通路等方式治疗IMN,可为后续研究提供参考.
Objective:To investigate the mechanism of action of Zhenwu decoction in the treatment of idio-pathic membranous nephropathy(IMN)based on network pharmacology and GEO database.Methods:TCMSP data-base was used to obtain the active components and targets of Zhenwu decoction,and four databases,including Gene-Cards,were used to obtain the targets of IMN.STRING database and Cytoscape software were used to construct a drug-component-target-disease interaction network and a protein-protein interaction network of core targets,and the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)path-way enrichment analysis were performed.Molecular docking was performed,and the analyses of differentially ex-pressed core target genes and immune cell infiltration were performed based on GEO database.Results:The key active components of Zhenwu decoction in the treatment of IMN included stigmasterol,kaempferol,and beta-sitos-terol,and the core targets included AKT1,JUN,and CASP3.The KEGG enrichment analysis showed that 117 signa-ling pathways were involved,including the fluid shear stress pathway.Molecular docking showed that kaempferol and beta-sitosterol showed strong binding activities to the targets such as PTGS2,CASP3,and AKT1.In the GSE115857 dataset,AKT1,intercellular adhesion molecule-1,and CASP3 were upregulated genes,and JUN was a downregulat-ed gene,which might be associated with the immune cells such as unactivated CD4 memory T cells and unactivated natural killer cells.Conclusion:Zhenwu decoction exerts a therapeutic effect on IMN through multiple components,targets,and pathways,which provides a reference for subsequent studies.

idiopathic membranous nephropathyZhenwu decoctionnetwork pharmacologytarget gene

尚宗杰、张少崇、王春芳、杨洪涛

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濮阳市中医医院,河南 濮阳,457000

天津中医药大学第一附属医院,天津,300381

特发性膜性肾病 真武汤 网络药理学 靶点基因

河南省卫生健康委员会中医药传承与创新人才工程

豫卫中医函[2021]15号

2024

湖南中医杂志
湖南省中医药研究院

湖南中医杂志

影响因子:0.484
ISSN:1003-7705
年,卷(期):2024.40(4)
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