运用数据挖掘及网络药理学探讨糖尿病皮肤瘙痒症中医用药规律及作用机制

Prescription rules and mechanism of TCM medicine in the treatment of diabetes pruritus based on data mining and network pharmacology

目的:探索中药方剂治疗糖尿病皮肤瘙痒症的用药规律,为临床组方用药提供参考。方法:运用中国知网、万方数据、维普期刊全文数据库检索中医药治疗糖尿病皮肤瘙痒症的文献,并对其进行筛选建立数据库,通过BM SPSS Modeler 18.0、SPSS Statistics 25.0进行数据挖掘,研究用药规律。通过检索中药系统药理学数据库与分析平台(TCMSP)、OMIM、Genecards、PharmGkb、Digsee数据库获得核心组方的有效成分及疾病靶点,利用Cytoscape 3.8.2软件构建“药物-有效成分-靶点-疾病”网络图,运用Stitch和String构建蛋白质-蛋白质相互作用网络,并对于网络拓扑分析获得核心靶点。筛选DAVID数据库对核心靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果:共纳入文献159篇,涉及中药处方215剂,获得高频中药24味,当归-白芍-防风、当归-白芍-生地黄、当归-白芍-蒺藜、当归-川芎等核心药对14组,聚类分析得到8类,通过因子分析获得9个公因子,核心组方有效成分功共169个,药物潜在靶点263个,疾病潜在靶点519个,核心靶点7个,共获得83条GO生富集功能及25条KEGG信号通路。结论:中医药治疗糖尿病皮肤瘙痒症以养血疏风、活血化瘀、补脾益肾为原则,其核心药物治疗本病多涉及胰岛素抵抗、炎症反应、氧化应激等。

Objective:To explore the medication rule of TCM prescription in treating diabetic pruritus,and provide reference for clinical medication.Methods:CNKI,Wanfang Data and VIP were used to search the literature of treating diabetic pruritus in TCM,after screening,a database was established.The data mining was carried out by SPSS Modeler 18.0 and SPSS Statistics 25.0 software to study the medication rule.TCMSP,OMIM,Genecards,PharmGkb and Digsee database were searched to obtain active ingredients of core drug combination and disease targets.Cytoscape 3.8.2 software was used to construct the“drugs-active ingredients-targets-diseases”network diagram.Stitch and String were used to construct the protein-protein interaction network,and the core targets were obtained by network topology analysis.DAVID database was screened for GO and KEGG enrichment analysis of core targets.Results:A total of 159 studies were included,215 prescriptions of TCM,and 24 high-frequency medicines were obtained,including 14 pairs of core combination such as Danggui(radix angelicae sinensis)-Baishao(radix paeoniae alba)-Fangfeng(radix saposhnikoviae),Danggui-Baishao-Shengdihuang(radix rehmanniae recens),Danggui-Baishao-Jili(fructus tribuli),Danggui-Chuanxiong(rhizoma ligustici chuanxiong),etc..There are 8 categories were obtained by cluster analysis,and 9 common factors were obtained by factor analysis,169 active ingredients in the core formula and 263 potential drug targets.There are 519 potential disease targets and 7 core targets,and a total of 83 GO enrichment functions and 25 KEGG signaling pathways have been obtained.Conclusion:The principle of nourishing blood and dispelling wind,promoting blood circulation and removing blood stasis,invigorating spleen and tonifying kidney are taken as the treatment of diabetic pruritus with TCM medicine,and its core drugs mostly involve insulin resistance,inflammatory reaction,oxidative stress and so on.