基于数据挖掘和网络药理学的肥胖用药规律及潜在作用分析

A study of the medication rule for obesity and its potential role based on data mining and network pharmacology

关键词:  肥胖  数据挖掘  网络药理学  用药规律  中药治疗

Key words:  obesity  data mining  network pharmacology  medication rule  Chinese herbal treatment

摘要:

[目的] 基于数据挖掘分析中药治疗肥胖的组方用药规律，并通过网络药理学方法分析高频药物治疗肥胖的潜在作用机制。[方法] 以中国知识资源总库（CNKI）、中国生物医学文献数据库（CBMdisc）、中文科技期刊数据库（VIP）、万方数据资源系统为资料来源。使用Excel 2016，统计学软件R3.5.2，对数据进行频数分析、关联规则分析、聚类分析及主成分分析，使用BATMAN-TCM系统对高频药物所含化合物进行检索，获取这些化合物对应靶点，与Genecard数据库中检索obesity相关靶点相映射并取交集，通过STRING 11.0构建PPI网络，对其进行网络拓扑分析，筛选出高频药物治疗肥胖病的核心靶点，通过DAVID 6.8数据库进行KEGG通路分析获取高频药物治疗肥胖病的重要通路。[结果] 筛选出符合排除与纳入标准的文献共143篇，其中收录中药组方148首、药物172味。通过分析处方中药物的使用频次、并进行关联规则分析、聚类分析以及主成分分析，得出药物使用频率≥ 10%的药物共21种，药物关联规则按支持度、置信度、提升度排序各6个药物组合，以及2个聚类药物群和主成分分析中4个主要维度的代表用药。通过网络药理学方法发现茯苓治疗肥胖病的核心靶点10个以及和肥胖病关系密切的通路20条。[结论] 中药治疗肥胖主要从"气虚""痰湿""血瘀"3个方面进行调治。以健脾利湿化痰为主要治则，故用药多以具有益气健脾，燥湿化痰功效的中药为主，辅以具有化瘀消脂作用之泽泻、山楂、丹参、荷叶等。初步验证和预测了高频药物茯苓治疗肥胖的核心靶点和重要通路，为深入研究其作用机制提供参考。

Abstract:

[Objective] To analyze the traditional Chinese medicine formula and medication rule for obesity based on data mining and to explore the potential mechanism of action of high-frequency drugs for the treatment of obesity by network pharmacology method.[Methods] Chinese National Knowledge Infrastructure (CNKI),China Biology Medicine disc (CBMdisc),VIP and Wanfang Data were used as the data sources. Frequency analysis,association rules analysis,cluster analysis and principal component analysis (PCA) were carried out on these data by using Excel 2016 and statistical software R3.5.2,and the compounds contained in high-frequency drugs were searched by using BATMAN-TCM system to obtain the targets corresponding to these compounds. These targets were mapped to obesity-associated targets searched in Genecard database and intersection elements were obtained for network topology analysis by building a PPI network based on STRING 11.0 to screen out the core targets of high-frequency drugs for the treatment of obesity. KEGG pathway was analyzed through DAVID 6.8 Database to obtain the important pathways of high-frequency drugs for obesity.[Results] A total of 143 literatures meeting the exclusion criteria were selected,and traditional Chinese medicine formulas and 172 drugs were included. Through the analysis of usage frequency of drugs in the prescriptions,association rules analysis,cluster analysis and PCA,twenty one drugs with a usage frequency of ≥ 10%,six drug combinations sorted in terms of support degree,confidence coefficient and upgrade degree of the drugs association rules prospectively,two cluster drug groups and representative medicines of 4 dimensions in PCA. Ten core targets of poria cocos for the treatment of obesity and 20 pathways closely associated with obesity were found by network pharmacology method.[Conclusion] In traditional Chinese medicine,the treatment of obesity focuses on the regulation of "qi deficiency","phlegm-dampness" and "blood stasis". The major principle of treatment is to invigorate spleen to remove dampness and reduce phlegm. Therefore,obesity is treated mainly with Chinese medicines aiming to replenish qi to invigorate the spleen and eliminate dampness and phlegm,as well as adjuvant drugs aiming to disperse blood stasis and lipid,such as rhizoma alismatis,hawthorn,salvia miltiorrhiza,lotus leaf,etc. We have preliminarily verified and predicted the core targets and important pathways of the high-frequency drug poria cocos for the treatment of obesity,providing reference for an in-depth study of its mechanism of action.