基于网络药理学与分子对接探讨脑积水方治疗正常压力性脑积水的机制  

Mechanism of hydrocephalus formula in treatment of alzheimer disease based on network pharmacology and molecular docking

作　　者：王一帆 田财军[1] WANG Yifan

机构地区：[1]山东中医药大学,山东济南250013

出　　处：《中医临床研究》2023年第32期23-29,共7页Clinical Journal Of Chinese Medicine

基　　金：山东省中医药科技发展计划(2019-0171);山东省中医药科技发展计划(2019-0044)。

摘　　要：目的:运用网络药理学与分子对接的方法探讨脑积水方治疗正常性压力脑积水(Normal Pressure Hydrocephalus,NPH)的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)检索并筛选出脑积水方的有效成分及作用靶点。通过在GeneCards数据库、DrugBank数据库、OMIM数据库检索出NPH相关靶点,使用韦恩图获得脑积水方药物与NPH的交集靶点。使用STRING 12.0数据库获得蛋白质-蛋白质相互作用网络信息。使用Cytoscape 3.7.2软件构建“药物-有效成分-靶点”网络图与蛋白质-蛋白质相互作用网络图,通过DAVID v6.8数据库对共同靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。使用SYBYL-X 2.1.1软件进行分子对接。结果:共筛选出脑积水方2中6个有效成分,56个药物与疾病交集靶点,核心靶点为肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-6(Interleukin-6,IL-6)、JUN原癌基因(Jun Proto-Oncogene,JUN)、前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)。GO功能分析主要涉及管生成、凋亡过程、胞外基质、细胞表面、白酶结合、蛋白质丝氨酸/苏氨酸/酪氨酸激酶活性等生物过程,KEGG分析主要涉及流体剪切应力与动脉粥样硬化、脂质与动脉粥样硬化、磷脂酰肌醇3激酶-蛋白激酶B(Phosphatidylinositol 3 Kinase-Akt,PI3K-Akt)信号通路、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)信号通路。分子对接结果显示,花生四烯酸与JUN、花生四烯酸与EGFR、花生四烯酸与IL-6、花生四烯酸与TNF、槲皮素与PTGS2之间有均有着较强的结合能力。结论:本研究初步阐释了脑积水方通过多成分、多靶点治疗NPH的潜在机制。Objective:To explore the mechanism of hydrocephalus prescription in treating normal pressure hydrocephalus(NPH)by using network pharmacology and molecular docking methods.Method:The active ingredients and targets of hydrocephalus prescription were searched and screened by TCMSP.NPH-related targets were retrieved from the GeneCards database,DrugBank database,and OMIM database,and the intersection targets of hydrocephalus prescription drugs and NPH were obtained using Venn diagrams.The protein-protein interaction(PPI)network information was obtained using the STRING 12.0 database.Using Cytoscape 3.7.2 software to build a drug-active ingredient-target network diagram and a PPI network diagram,the common targets were analyzed by GO and KEGG through the DAVID v6.8 database.Molecular docking was performed using SYBYL-X 2.1.1 software.Results:A total of 26 active ingredients and 56 drug-disease intersection targets were screened out,and the core targets were TNF,IL-6,JUN,PTGS2,and EGFR.GO functional analysis mainly involves biological processes such as tube formation,apoptosis process,extracellular matrix,cell surface,leukin binding,protein serine/threonine/tyrosine kinase activity,etc..KEGG analysis mainly involves fluid shear stress and atherosclerosis,lipid and atherosclerosis,PI3K-Akt signaling pathway,and MAPK signaling pathway.The molecular docking results showed that arachidonic acid and JUN,arachidonic acid and EGFR,arachidonic acid and IL-6,arachidonic acid and TNF,quercetin and PTGS2 all had strong binding abilities.Conclusion:This study preliminarily explained the potential mechanism of hydrocephalus formula in treating NPH through multi-components and multi-targets.

关 键 词：网络药理学 分子对接 正常压力性脑积水 脑积水方 

分 类 号：R331[医药卫生—人体生理学]