基于网络药理学探索丹参治疗膜性肾小球肾炎的作用机制
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作者:朱永秋 张法荣
摘要 目的:采用网络数据挖掘方法研究丹参对膜性肾小球肾炎(MGN)的作用机制。方法:运用中药系统药理数据库和分析平台(TCMSP)及与疾病相关的人类孟德尔遗传数据库(OMIM)、DrugBank、DisGeNET数据库分别检索筛选,获得丹参的有效活性成分、药物作用靶点及MGN的相关靶点,运用Cytoscape 3.7.2构建丹参-成分-靶点网络,并根据自由度筛选出核心成分。采用STRING软件构建蛋白质-蛋白质相互作用(PPI)网络,并在Cytoscape 3.7.2平台进行拓扑分析并筛选出关键靶点。使用基因注释工具MetascapeΠ械慊因进行注释和分析,得到靶点的生物过程和通路富集结果。结果:共获得65个丹参有效活性成分,99个目标靶点,与MGN相关的靶点15个,关键靶点8个。得到肾上腺素受体、MAPK级联的正调控、细胞阳离子稳态、激素水平的调节、跨膜转运的调控等9条生物过程和通路富集分析。结论:传统中草药丹参活性成分对MGN的作用机制体现了丹参多成分、多靶点、多途径作用的特点,为丹参治疗MGN的作用机制阐明提供了依据,并为中药的作用机制研究提供参考思路。
关键词 网络药理学;丹参;活性成分;活血化瘀;膜性肾小球肾炎;多靶点;肾上腺素能受体;机制
Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Membranous Glomerulonephritis Based on Network Pharmacology
ZHU Yongqiu1,ZHANG Farong2
(1 Shandong University of Traditional Chinese Medicine,Ji′nan 250014,China; 2 Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji′nan 250014,China)
Abstract Objective:To study the mechanism of Salviae Miltiorrhizae Radix et Rhizoma(SMR) in the treatment of membranous glomerulonephritis(MGN) by network pharmacology and data mining.Methods:The active components and targets of SMR and MGN targets were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Online Mendelian Inheritance in Man(OMIM),DrugBank,and DisGeNET.Cytoscape 3.7.2 was used to construct an SMR-component-target network,and the core components were screened out according to the degree of freedom.The protein-protein interaction(PPI) network was constructed by STRING,and the key targets were selected through topological analysis on the platform of Cytoscape 3.7.2.The target genes were annotated and analyzed by Metascape,and the biological processes and pathway enrichment results were obtained.Results:Sixty-five active components of SMR,99 targets,15 MGN-related targets,and eight key targets were obtained.Nine biological processes and pathways,including adrenoceptors,positive regulation of MAPK cascade,cellular cation homeostasis,regulation of hormone levels,and regulation of transmembrane transport,were analyzed.Conclusion:The mechanism of SMR active components on MGN embodies the multi-component,multi-target,and multi-pathway characteristics of SMR,which provides the basis for clarifying the mechanism of SMR in the treatment of MGN and ideas for the research on the mechanism of Chinese medicine.
Keywords Network pharmacology; Salviae Miltiorrhizae Radix et Rhizoma; Active components; Activating blood and resolving stasis; membranous glomerulonephritis(MGN); Multiple targets; Adrenoceptor; Mechanism
nlc202207141850
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