基于数据挖掘和网络药理学收集的国家专利复方治疗肝硬化腹水作用机制分析

Analysis of the mechanism of national patent compound in treating cirrhotic ascites based on data mining and network pharmacology

目的:运用现代技术挖掘治疗肝硬化腹水的国家专利中药复方药物,分析其用药规律及核心药对治疗肝硬化腹水的作用机制。方法:通过国家知识产权数据库检索收集治疗肝硬化腹水的中药复方,运用Excel 2019、SPSS Modeler 18.0和SPSS Statistics 23.0软件,分别进行用药频次分析、关联规则分析、因子分析并获取核心药对。通过检索TCMSP、SymMap、Pharmmapper、UniProt、OMIM、GeneCards、DrugBank等数据库,取得核心药对的活性成分,预测核心药对的药物靶点,收集肝硬化腹水的疾病相关靶点,运用Cytoscape 3.7.2软件进行拓扑分析获得核心药对治疗肝硬化腹水的核心靶点。将核心药对和肝硬化腹水的交集靶点提交至David数据库进行GO及KEGG富集分析。结果:有139首国家专利中药复方被纳入,整理出500味中药,经过频次分析得出前10位的高频药物分别为茯苓、白术、泽泻、大腹皮、丹参、黄芪、茵陈、柴胡、厚朴、车前子。以支持度≥7.5%、置信度≥80%、增益>1为设置条件进行关联规则分析,从因子分析中提取13个公因子,得出置信度及因子贡献率最高的核心药对为莪术-三棱。网络药理学分析结果,共筛选出17个药物化学成分、396个药物靶点及1109个疾病靶点,其中药物-疾病交集靶点112个。经过GO富集分析得出381个生物学过程、41个细胞组分、94个分子功能,KEGG富集分析得出109条信号通路。结论:近代医家在运用祖国医学治疗肝硬化腹水过程中多以补气、化瘀、行气、利水为主。预测莪术-三棱可通过白蛋白(Alb)等多个核心靶点治疗肝硬化腹水,且靶点间相互存在着协同作用。莪术-三棱可通过干预癌症通路、催乳素信号通路、PI3K-Akt信号通路、VEGF信号通路等通路而起到治疗肝硬化腹水的作用。

Objective:To explore the drugs of national patented Chinese herbal compounds in the treatment of ascites due to liver cirrhosis by modern technology and analyze its medication regularity and the mechanism of core drugs in the treatment of ascites due to liver cirrhosis.Methods:The Chinese herbal compounds for the treatment of ascites due to liver cirrhosis were collected by searching the national intellectual property database.Excel2019,SPSS Modeler 18.0,and SPSS Statistics 23.0 software were used to analyze the frequency of medication,association rule analysis,factor analysis,and obtain the core drug pairs,respectively.By searching TCMSP,SymMap,Pharmmapper,UniProt,OMIM,GeneCards,DrugBank,and other databases,the active components of the core drug pair were obtained,the drug targets of the core drug pair were predicted,the disease-related targets of cirrhotic ascites were collected,and the core targets of the core drug pair for the treatment of cirrhotic ascites were obtained by topological analysis using Cytoscape3.7.2 software.The intersection targets of core drug pairs and cirrhotic ascites were submitted to the David database for GO and KEGG enrichment analysis.Results:A total of 139 national patented Chinese herbal compounds were included,500 herbs were sorted out,and the top 10 high-frequency drugs were:Poria cocos,Atractylodes macrocephala,Alisma orientalis,Areca peel,Radix salviae,Astragalus membranaceus,Artemisiae scopariae,Radix bupleuri,Magnolia officinalis,and Plantaginis semen.Association rule analysis was performed using support≥7.5%,confidence≥80%,and gain>1 as setting conditions,and 13 common factors were extracted from factor analysis,and it was concluded that the core drug pair with the highest confidence and factor contribution rate was Curcuma zedoaria-trigonella.According to the results of network pharmacological analysis,a total of 17 medicinal chemical components,396 drug targets,and 1109 disease targets were selected,including 112 drug-disease intersection targets.After GO enrichment analysis,381 biological processes,41 cellular components,and 94 molecular functions were obtained,and KEGG enrichment analysis resulted in 109 signaling pathways.Conclusion:Modern physicians in the use of the motherland medicine in the treatment of liver cirrhosis ascites in the process of invigorating qi,transforming stasis,move qi,disinhibit water.It is predicted that Curcuma zedoaria-Sanleng can treat cirrhotic ascites through multiple core targets such as albumin(Alb),and there is a synergistic effect between the targets.Curcuma-Sanleng can treat cirrhotic ascites by intervening in the cancer pathway,prolactin signaling pathway,PI3K-Akt signaling pathway,VEGF signaling pathway,and other pathways.