基于网络药理学和分子对接探讨柴胡生地黄治疗特发性膜性肾病的作用机制  

A study on the action mechanism of Chaihu and Sheng Dihuang on idiopathic membranous nephropathy based on network pharmacology and molecular docking technology

作　　者：李小娟 肖振卫[2] LI Xiaojuan

机构地区：[1]山东中医药大学第一临床医学院,山东济南250000 [2]山东中医药大学附属医院,山东济南250000

出　　处：《中医临床研究》2022年第26期1-5,共5页Clinical Journal Of Chinese Medicine

基　　金：山东中医药大学专业学位研究生教学案例库建设项目:肾脏疾病教学案例库的构建与应用研究(XJAL2021002)。

摘　　要：目的:运用网络药理学和分子对接探讨柴胡生地黄治疗特发性膜性肾病(Idiopathic Membranous Nephropathy,IMN)的作用机制。方法:检索中药系统药理学数据库与分析平台、中医药综合数据库及文献报道筛选柴胡生地黄有效成分,利用SwissTargetPrediction预测潜在靶点。利用Genecards、OMIM及Drugbank检索IMN靶点,通过Venny获取药物作用靶点与疾病靶点的交集。利用STRING构建蛋白质相互作用网络,利用Metascape进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,利用Autodock对有效成分与关键靶点进行分子对接。结果:柴胡生地黄治疗IMN的核心有效成分为槲皮素、山柰酚、异鼠李素、阿魏酸甲酯、3,5,6,7-四甲氧基-2-(3,4,5-三甲氧基苯基)色酮等,核心靶点为白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/threonine Protein Kinase 1,AKT1)、信号转导和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、表皮生长因子(Epidermal Growth Factor,EGF)、肿瘤蛋白P53(Tumor Protein P53,TP53)等。共得到炎症反应、活性氧代谢过程、积极的调节细胞的能动性等1744个GO富集结果和糖尿病并发症中的晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、内分泌阻力、T细胞受体信号通路等235条KEGG通路。分子对接显示有效成分与靶蛋白结合能均<0。结论:柴胡生地黄通过多成分、多靶点、多信号通路实现对IMN的治疗作用。Objective:To investigate the action mechanism of Chaihu(radix bupleurum)and Sheng Dihuang(rehmanniae)on IMN by network pharmacology and molecular docking technology.Methods:TCMSP,TCMID and literature reports were searched to screen the effective components of Chaihu and Sheng Dihuang.SwissTargetPrediction database was used to obtain potential targets.The IMN targets were acquired by Genecards,OMIM and Drugbank.The intersection of drug active ingredient targets and disease gene targets was obtained by Venny.Protein-protein interaction network was constructed by STRING.The GO functional analysis and KEGG pathways enrichment analysis were performed by Metascape.Molecular docking between active components and key targets was performed by Autodock.Results:The core effective components of Chaihu and Sheng Dihuang on IMN were penetin,shandonol,isorhamnetin,methyl ferulate,3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxy-phenyl)tryptophan and so on.The core targets were IL-6,VEGFA,AKT1,STAT3,EGF,TP53,and so on.A total of 1744 GO enrichment results such as inflammatory response,reactive oxygen species metabolic process,and positively regulates cell motility,and 235 KEGG pathways enrichment results such as advanced glycation end products-advanced glycation end products receptor in diabetic complications signaling pathway,endocrine resistance,and T cell receptor signaling pathway were obtained.The results of molecular docking showed that the binding energies of the active components and the key targets were all less than 0.Conclusion:Chaihu and Sheng Dihuang has therapeutic effect on IMN through multi-component,multi-target and multiple signal pathways.

关 键 词：网络药理学 柴胡 生地黄 特发性膜性肾病 分子对接 

分 类 号：R256.5[医药卫生—中医内科学]