运用数据挖掘和网络药理学探讨糖尿病认知功能障碍中医用药规律和作用机制

Prescription rules and mechanism of core drugs in the treatment of diabetic cognitive dysfunction based on data mining and network pharmacology

本文旨在通过探讨中医药治疗糖尿病认知功能障碍的用药特点与规律,为临床用药提供新的参考。运用中国知网(CNKI)、万方数据(WF)、维普期刊全文数据库(VIP)、生物医学文献数据库(CBM)、及中国科学引文数据库(CSCD)检索自1999年1月至2020年10月收载的中医药治疗糖尿病认知功能障碍文献,经筛选后建立数据库,运用Microsoft Excel 2019、SPSS Modeler 18.0、SPSS Statistics 25.0软件进行数据挖掘,分析用药规律。通过检索TCMSP、OMIM、TTD、Pharm Gkb和Drugbank数据库获得核心药物组合和疾病的有效活性成分,利用Cytoscape 3.8.0软件构建“化合物-靶点”作用网络图,运用Stitch和String构建蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape进行网络拓扑分析获得药物和疾病交互的核心靶点。筛选DAVID数据库对核心靶点进行GO和KEGG富集分析。结果共纳入文献33篇,中药处方123首,获得高频中药20味,桃仁-红花、当归-桃仁-川芎、熟地黄-菟丝子-枸杞子等26对核心药物组合,通过因子分析提取8个公因子,聚类分析得到6类,得到核心组方的有效活性成分109个,药物潜在基因靶点1620个,疾病潜在基因靶点1490个,核心组方治疗疾病的核心靶点76个,涉及237条GO富集功能和96条KEGG通路。发现中医治疗糖尿病认知功能障碍以活血化瘀、化痰开窍、滋益固肾为原则,其核心药物治疗糖尿病认知功能障碍的作用机制可能与胰岛素抵抗、细胞凋亡、炎症反应、内质网应激等密切相关。

To explore the characteristics and rules of traditional Chinese medicine(TCM)in the treatment of diabetic cognitive dysfunction,and to provide new references for clinical medication.Methods:The Chinese Knowledge Network(CNKI),Wanfang Data(WF),Weipu Journal Full-text Database(VIP),China biology medicine disc(CBM),and Chinese Science Citation Database(CSCD)were retrieved from 1999 to October 2020.The contained literature on the treatment of diabetic cognitive dysfunction with traditional Chinese medicine,after screening,establish a database,use Microsoft Excel 2019,SPSS Modeler 18.0,SPSS Statistics 25.0 software for data mining,and analyze the distribution and regularity of drug efficacy.Through searching TCMSP,OMIM,TTD,Pharm Gkb and Drugbank database to obtain the core drug combination and the effective active ingredients of the disease,using Cytoscape 3.8.0 software to construct the"compound-target"interaction network diagram,using Stitch and String to construct the protein-protein interaction(PPI)network,and use Cytoscape to perform network topology analysis to obtain the core target of drug and disease interaction.Screen the DAVID database for GO and KEGG enrichment analysis of core targets.Results:A total of 33 articles were included,123 Chinese medicine prescriptions,and 20 high-frequency Chinese medicines were obtained,including 26 pairs of core drug combinations such as Persicae Semen-Carthami Flos,Angelicae Sinensis Radix-Persicae Semen-Chuanxiong Rhizoma,Rehmanniae Radix Praeparata-Cuscutae Semen-Lycii Fructus,etc.There are 8 common factors and 6 categories of cluster analysis,109 active ingredients of the core formula,1620 potential drug targets,1490 potential disease gene targets,and the core formula treats diseases There are 76 core targets,involving 237 GO enrichment functions and 96 KEGG pathways.TCM treats diabetes cognitive dysfunction mainly by promoting blood circulation,removing blood stasis,nourishing qi and nourishing yin.The mechanism of its core drugs in the treatment of diabetic cognitive dysfunction may be related to insulin resistance,apoptosis,inflammation,endoplasmic reticulum stress is closely related.