基于数据挖掘和网络药理学探究补肾活血法治疗血管性痴呆作用机制  

Study on the Action Mechanism of the Treatment Principle of Tonifying Kidney and Promoting Blood Circulation with Vascular Dementia Based on Data Mining and Network Pharmacology

作　　者：梁鸣展 张彬彬 刘光辉[1,3] 张林[1] 殷晓梅[1] 王艳杰[1] 方德宇[1] 李硕[1] 倪菲[1] LIANG Mingzhan;ZHANG Binbin;LIU Guanghui;ZHANG Lin;YIN Xiaomei;WANG Yanjie;FANG Deyu;LI Shuo;NI Fei(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;79th Army Hospital,Hospital,Liaoyang 111000,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳1108472 [2]陆军第79集团军医院,辽宁辽阳111000 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《辽宁中医药大学学报》2022年第5期139-147,共9页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金(20180550374);辽宁中医药大学大学生创新创业训练计划(201910162035);。

摘　　要：目的运用数据挖掘和网络药理学研究方法,探究基于补肾活血治疗原则运用中医药治疗血管性痴呆(vascular dementia,VaD)的用药规律及潜在作用机制。方法将1996年—2021年中国知网、万方数据知识服务平台、维普数据库中检索到有关补肾活血法治疗VaD的临床研究文献作为数据来源,利用古今医案云平台在线分析软件及SPSS Modeler 18.0对文献中记载的复方药物进行频次分析、关联分析并获取核心药物组合;通过中药系统药理学数据库及分析平台TCMSP、中医药证候关联数据库SymMap、中医药百科全书数据库ETCM、TargetNet数据库检索核心药物的有效成分及作用靶点,比较毒物基因组学数据库CTD、基因组注释数据库平台GeneCards数据库检索疾病相关靶点,并通过uniprot数据库对获得的作用靶点进行规范化处理,对得到的化合物成分进行GO、KEGG富集分析,运用Cytoscape构建药物-成分-靶点-通路及PPI蛋白相互作用网络,并使用AutoDock Vina进行分子对接验证。结果经筛选得到92篇文献,共计92首方剂,97味中药,熟地黄、何首乌、石菖蒲、川芎作为核心药物组合。其中核心药组有效成分共计23种,靶点273个,与VaD高度关联的靶点包括APP、TNF、JUN,其作用机制可能通过调控cAMP、MAPK、雌激素、神经营养因子、流体剪切应力和动脉粥样硬化通路来实现。分子对接结果显示,核心药物组合有效成分Questin与TNF、Polygonimitin B与APP、Emodin与JUN对接良好。结论熟地黄、何首乌、石菖蒲、川芎作为补肾活血法治疗VaD的核心药物组合,其作用机制可能是通过作用cAMP、MAPK、雌激素、神经营养因子、流体剪切应力和动脉粥样硬化通路实现。该研究初步探讨了补肾活血法治疗VaD的主要物质基础及潜在作用机制,总结了该治法在临床中的一般用药规律,为今后进一步研究中医药治疗VaD提供参考。Objective To explore the medication rules and potential action mechanism of TCM in the treatment of vascular dementia(VaD)with the treatment principle of tonifying kidney and promoting blood circulation,by using methods of data mining and network pharmacology.Methods Creating the data source includes clinical research literatures about the treatment of VaD by using the treatment principle of tonifying kidney and promoting blood circulation which can be retrieved from CNKI,WanFang Data Knowledge Service Platform and VIP database from 1996—2021,using online analysis software ancient and modern medical case cloud platform and SPSS Modeler 18.0 to conduct frequency analysis and association analysis of compound drugs recorded in the literature and obtain the core drug combination.Get the active ingredients and action targets of core drugs from database TCMSP,SymMap,ETCM,TargetNet,disease-related targets were retrieved from CID and GeneCards databases,normalizing these targets by using database uniport.The obtained drugs component targets enriched by GO and KEGG enrichment analysis,construct the network includes drug,component,target,pathway and network PPI through Cytoscape software,AutoDock Vina is used for molecular docking.Results After screening,92 literatures were obtained,including 92prescriptions and 97 drugs,Shudihuang(Rehmanniae Radix Praeparata),Heshouwu(Polygoni Multiflori Radix),Shichangpu(Acori Tatarinowii Rhizoma),Chuanxiong(Chuanxiong Rhizoma)were used as core drug combination.23 active components and 273 targets were found in this core drug combination,APP,TNF,JUN were highly associated with VaD,the mechanism of action may associate with regulating cAMP,MAPK,estrogen,neurotrophic factor,fluid shear stress and atherosclerosis pathway.Molecular docking result shows Questin,Polygonimitin B,Chrysophanol-9-Anthrone were mainly interacted with TNF,APP,JUN.Conclusion As the core drug combination of the treatment principle of tonifying kidney and promoting blood circulation,Shudihuang(Rehmanniae Radix Praepa

关 键 词：数据挖掘 网络药理学 分子对接 补肾活血法 血管性痴呆 

分 类 号：R285.5[医药卫生—中药学]