基于数据挖掘与网络药理学探析王雪峰教授运用中药治疗小儿脑瘫用药规律及作用机制

Exploration of Professor WANG Xuefeng's the Rule and Mechanism of TCM Treatment of Pediatric Cerebral Palsy Based on Data Mining and Network Pharmacology

目的运用数据挖掘和网络药理学技术探究王雪峰教授运用中药治疗小儿脑瘫的用药规律和潜在作用机制。方法通过Excel、OriginPro 2021、IBM SPSS Modeler 18.0等软件整合王雪峰教授近年临床医案,对其进行数据挖掘,总结核心处方及用药规律;将核心处方通过BATMAN-TCM、GeneCards、OMIM、TTD等数据库提取核心药物和疾病的潜在基因靶点,通过Venny 2.1.0提取交集基因,其结果依次进行蛋白互作网络(protein-protein interaction,PPI)分析,基因本体分析以及信号通路富集分析,最后通过Cytoscape 3.7.2构建“药物-成分-靶点-通路-疾病”网络。结果共纳入临床医案97则,涉及辨证论治处方97个,中药126味,其中21味高频中药,性味以温、甘、辛为主,主要归脾、肝、肺经;聚类分析得到5个有效聚类群;关联分析得到113条关联规则,并总结出王雪峰教授治疗脑瘫的核心处方为“白芍-甘草-大枣-黄芪-桂枝-茯苓”;核心处方有效活性成分158个,涉及基因靶点621个,疾病靶点974个,药物与疾病交集靶点67个;PPI网络分析共得到67个节点,304条边,平均节点度值9.07;基因本体(gene ontology,GO)分析中涉及生物过程(biological process,BP)229条,细胞组成(cellular component,CC)57条,分子功能(molecular function,MF)59条。京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)分析出71条信号通路;复杂网络分析共有793个节点,2107条边,度值阈值为5.314,平均度值2.03。茯苓酸B(Poricoic Acid B)、芍药内酯苷(Albiflorin)以及乳酸菌素(Lactiflorin)可能是治疗脑瘫发挥关键作用的活性成分。结论王雪峰教授治疗脑瘫从肝脾论治,以补虚扶正、和血通痹为治疗大法,选用黄芪桂枝五物汤为底方临证加减疗效确切,有理可依,有据可循。

Objective To explore the traditional Chinese medicial rule and potential mechanisms of Professor WANG Xuefeng's traditional Chinese medicine in the treatment of pediatric cerebral palsy based on data mining and network pharmacology technology.Methods Through integrating Professor WANG Xuefeng's recent clinical medical cases through software such as Excel,OriginPro 2021,IBM SPSS Modeler18.0,and conduct data mining to summarize core prescriptions and medication rules;The core prescription was extracted from potential gene targets of core drugs and diseases through BATMAN-TCM,GeneCards,OMIM,TTD and other databases,and the intersection genes were extracted through Venny2.1.0.The results were analyzed by PPI interaction network,Gene Ontology analysis,and signal pathway enrichment analysis in turn.Finally,the“drug component target pathway disease”network was constructed through Cytoscape 3.7.2.Results A total of 97 clinical medical records were included,involving 97 prescriptions for syndrome differentiation and treatment,and 126 traditional Chinese medicines.Among them,21 high-frequency traditional Chinese medicines were mainly characterized by warm,sweet and hot,mainly concentrated in the spleen,liver,and lung meridians;Cluster analysis yielded 5 effective cluster groups;The association analysis obtained 113 association rules and summarized that Professor WANG Xuefeng's core prescription for treating cerebral palsy was“Baishao(Paeoniae Radix Alba)-Gancao(Glycyrrhizae Radix Et Rhizoma)-Dazao(Jujubae Fructus)-Huangqi(Astragali Radix)-Guizhi(Cinnamomi Ramulus)-Fulingpi(Poriae Cutis)”;There were 158 effective active ingredients in the core prescription,involving 621 gene targets,974 disease targets,67 drug disease intersection targets;The PPI network analysis obtained a total of 67 nodes and 304 edges,with an average node degree value of 9.07;In the GO analysis,there were 229 items related to BP,57 items related to CC,and 59 items related to MF.KEGG analyzed 71 signal pathways;There were a total of 793 nodes and 2107 edges in complex network analysis,with a degree threshold of 5.314 and an average degree value of 2.03.Pachymic acid B,Albiforin and Lactiflorin may be the active ingredients that play a key role in the treatment of cerebral palsy.Conclusion Professor WANG Xuefeng's treatment of cerebral palsy is based on the treatment of the lover and spleen,with the main methods of tonifying deficiency and strengthening the body,and promoting blood circulation to relieve obstruction.She selected Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤)as the base formula for clinical treatment,and the therapeutic effect is accurate,reasonable,and evidence-based.