基于网络药理学和分子对接探讨尿C方治疗IgA肾病作用机制  

Mechanism of Urine C Prescription in Treating IgA Nephropathy Based on Network Pharmacology and Molecular Docking

作　　者：张涤 李慧洁 邓跃毅[1] ZHANG Di;LI Huijie;DENG Yueyi(Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200030

出　　处：《新中医》2024年第5期187-199,共13页New Chinese Medicine

基　　金：上海市临床重点专科建设项目(shslczdzk04201)。

摘　　要：目的:通过网络药理学探讨尿C方治疗IgA肾病(IgAN)的关键成分和作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、PubChem、Swiss ADEM和SwissTargetPrediction获得尿C方作用靶点;应用Cytoscape 3.9.1软件构建“药物-成分-靶点”相互作用网络;通过GeneCards、OMIM和DisGeNET平台获得IgAN作用靶点;通过Venn 2.1制作韦恩图获得尿C方和IgAN之间的交叉靶点并进行鉴定和可视化,并利用STRING数据库建立蛋白质-蛋白质相互作用网络(PPI);借助DAVID数据库对交集靶点进行GO和KEGG富集分析并运用微生信在线平台对交集靶点进行GO和KEGG富集分析可视化;使用Autodock Vina软件进行分子对接验证,并利用PyMol软件得出对接结果。结果:共筛选得到尿C方有效成分70种及对应1 363个作用靶点,其中确定了10个关键活性成分。IgAN相关靶点1 593个,除重复项后获得823个疾病靶点,交集靶点111个。GO富集分析得到706个BP条目,63个CC条目,123个MF条目。KEGG富集分析得到161条与IgAN显著相关的通路。分子对接结果表明,核心活性成分与核心靶点之间存在较强的结合活性。结论:尿C方治疗IgAN的作用机制可能是通过槲皮素、山奈酚、β-谷甾醇、黄芩素等调控AGE-RAGE信号通路、IL-17信号通路、脂质和动脉粥样硬化等发挥治疗作用。Objective:To explore the key components and mechanism of Urine C Prescription in treating IgA nephropathy(lgAN)based on network pharmacology.Methods:The targets of Urine C Prescription were obtained by Traditional Chinese Medicine Systems Pharmacology Platform(TCMSP),PubChem,Swiss ADEM and Swiss Target Prediction.The "medicines-components-targets"interaction network was constructed via Cytoscape 3.9.1 software.The lgAN action targets were obtained by GeneCards,OMIM and DisGeNET platforms.The intersection targets between Urine C Prescription and IgAN were identified and visualized by Venn 2.1,and protein-protein interaction(PPl)network was established by STRING database.The intersection targets Were given GO and KEGG enrichment analysis by DAVID database and were visualized under GO and KEGG enrichment analysis through Bioinformatics online platform.Autodock Vina software was used to verify molecular docking,and PyMol software was used to obtain docking results.Results:A total of 70 kinds of active components and 1363 corresponding action targets of Urine C Prescription were selected,among which 10 key active components were identified.There were 1593 lgAN-related targets,and after removing the duplicate targets,823 disease targets and 111 intersection targets were obtained.GO enrichment analysis yielded 706 BP items,63 CC items and 123 MF items.KEGG enrichment analysis showed that 161 pathways were significantly correlated with IgAN.The results of molecular docking showed that there was strong binding activity between the core active components and the core targets.Conclusion:The mechanism of Urine C Prescription in treating IgAN may be the regulation of AGE-RAGE signaling pathway,IL-17 signaling pathway,lipid and atherosclerosis pathway through quercetin,kaempferol,β-sitosterol and baicalein.

关 键 词：IGA肾病 尿C方 网络药理学 分子对接技术 信号通路 

分 类 号：R285[医药卫生—中药学]