基于R语言数据挖掘和网络药理学探讨裴正学教授治疗原发性支气管肺癌的用药规律及临床经验

Professor PEI Zhengxue’s medication rules and clinical experience in treating lung cancer based on R language data mining and network pharmacology

目的:基于R语言数据挖掘技术分析裴正学教授治疗原发性支气管肺癌(简称肺癌)的用药及组方规律,基于网络药理学和分子对接技术探析核心组方的药理学机制。方法:收集裴正学教授治疗肺癌的门诊处方,建立“肺癌处方用药数据库”,通过对其进行频数、性味、关联规则及层次聚类分析探讨核心处方;基于网络药理学及分子对接技术揭示核心方剂治疗肺癌的主要成分、核心靶点及关键通路。结果:①共纳入处方98首,涉及药味212味,高频药物以燥湿化痰药、止咳平喘药为主,药性以温性和寒性为主,药味以苦味和辛味为主,归经以肺、脾经为主,通过关联规则及层次聚类分析得出苦杏仁、紫苏叶、半夏、陈皮、茯苓、桔梗、前胡、枳壳为核心方剂。②网络药理学分析共得出活性成分87个,核心成分有β-谷甾醇、槲皮素、木犀草素、柚皮素、川陈皮素等;潜在靶点262个,核心靶点144个;基因本体论(GO)和京都基因与基因组百科全书(KEGG)结果显示核心靶标富集在6538个GO功能及261条生物通路上,如磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(Akt)通路、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1通路、叉头框蛋白O(Forkhead Box Protein O,FoxO)信号通路、核因子-κB(Nuclear Factor-κB,NF-κB)通路等;分子对接结果显示核心成分与核心靶点对接活性良好。结论:裴正学教授治疗肺癌以“培土生金”为基本大法,寒温并举,辛苦并行,核心方剂杏苏散“苦杏仁、紫苏叶、半夏、陈皮、茯苓、桔梗、前胡、枳壳”通过多成分、多靶点、多通路协同调控发挥治疗作用;治则注重分期论治,宣降肺气,培土生金贯穿于治疗始终,重视肝脾肾三脏,擅用活血化瘀法,攻补兼施,遣方不拘一格,中晚期肺癌则以扶正固本为其治疗大法,在临床上取得了一定的疗效。

Objective:To analyze professor PEI Zhengxue’s medication rule and prescription composition law in the treatment of lung cancer based on R language data mining,to explore the pharmacological mechanism of core prescription based on network pharmacology and molecular docking technology.Methods:Collecting professor PEI Zhengxue’s outpatient prescriptions for lung cancer treatment and establishing lung cancer prescription drug database,the core prescriptions were analyzed by frequency,association rules and system cluster analysis.The main components,core targets and key pathways of core prescriptions in lung cancer treatment were revealed based on network pharmacology and molecular docking technology.Results:①A total of 98 prescriptions and 212 medicines were included.High-frequency medicines are mainly the Zaoshi Huatan medicines(燥湿化痰药),the Zhike Pingchuan medicines(止咳平喘药),the medicinal properties are mainly warm and cold,the medicinal taste is mainly bitter and spicy,and the lung and spleen meridians are the main ones,and Kuxingren(Semen Armeniacae Amarum)、Zisuye(Folium Perillae)、Banxia(Rhizoma Pinelliae)、Chenpi(Pericarpium Citri Reticulatae)、Fuling(Poria)、Jiegeng(Radix Platycodonis)、Qianhu(Radix Peucedani)、Zhike(Fructus Aurantii)are the core formulas through correlation rules and hierarchical clustering analysis.②A total of 87 active ingredients and 262 potential targets were obtained by network pharmacological analysis,the core components wereβ-sitosterol,quercetin,luteolin,naringin and nobiletin,the core targets were 144.GO and KEGG results showed that the core targets were enriched in 6538 GO processes and 261 biological pathways,such as PI3K/Akt pathway,HIF-1 pathway,FoxO signaling pathway,NF-κB pathway,etc..The molecular docking results showed that the core components had good docking activity with the core target.Conclusion:Professor PEI Zhengxue treats lung cancer with cultivating native gold as the basic method,combining cold and Wen(温),use together Xin(辛)and Ku(苦),and the core formula Kuxingren,Zisuye,Banxia,Chenpi,Fuling,Jiegeng,Qianhu,Zhike plays a therapeutic role through multi-component,multi-target,multi-pathway synergistic regulation.The treatment pays attention to the treatment of stages,declares the reduction of lung Qi(气),cultivates native gold throughout the treatment,attaches importance to the liver,spleen and kidneys,is good at using the method of activating blood circulation and removing stasis,attacking and supplementing,and the prescription is eclectic,and the middle and advanced lung cancer is based on Fuzheng Guben(扶正固本)as its treatment method,and has achieved certain clinical curative effects.