基于数据挖掘与网络药理学探讨李建生治疗慢性阻塞性肺疾病的用药规律及作用机制

Exploring the Medication Rules and Mechanism of Li Jiansheng in Treating Chronic Obstructive Pulmonary Disease Based on Data Mining and Network Pharmacology

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摘要目的采用数据挖掘方法分析李建生教授治疗慢性阻塞性肺疾病(COPD)的用药规律,并采用网络药理学方法探讨筛选出的核心中药组合治疗COPD的潜在作用机制。方法收集2014年11月至2024年3月李建生教授门诊治疗COPD的有效医案;采用频次分析、关联规则和层次聚类分析方法分析李建生教授治疗COPD的用药规律,并筛选出核心中药组合。采用网络药理学和分子对接技术探讨核心中药组合治疗COPD的潜在作用机制。结果(1)共筛选出375首处方,涉及179味中药。李建生教授治疗COPD常用的中药有人参、茯苓、半夏、浙贝母和厚朴等,药性以温、寒性为主;中药以苦、辛、甘味居多;多归于肺、脾、胃和肾经。关联规则分析得到茯苓-人参、浙贝母-人参、茯苓-半夏-人参等药物组合;层次聚类分析得到人参-茯苓-半夏-浙贝母-厚朴、陈皮-紫苏子-紫苏梗-款冬花-射干-紫菀等5个组方;筛选出核心中药组合为人参-茯苓-半夏-浙贝母-厚朴。(2)网络药理学分析获得核心中药组合治疗COPD的潜在靶点84个,其中核心靶点为细胞肿瘤抗原p53(TP53)、转录因子Jun(JUN)、肿瘤坏死因子(TNF)、RAC丝氨酸/苏氨酸蛋白激酶α(AKT1)、雌激素受体(ESR1)、转录因子p65(RELA)、蛋白激酶催化亚基C-α(PRKACA)、白细胞介素1β(IL-1β)、热休克蛋白90β(HSP90AB1)等10个靶点;主要活性成分有β-谷甾醇、山柰酚、豆甾醇等10个成分。核心中药组合治疗COPD的作用机制与脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路、TNF信号通路和化学致癌-受体激活等信号通路有关。分子对接结果显示,核心靶点与主要活性成分的结合活性良好。结论李建生教授治疗COPD以“正虚积损”为主要病机,形成了“调补肺肾、清化宣降”的特色疗法。核心中药组合(人参-茯苓-半夏-浙贝母-厚朴)的主要活性成分黄芩素、蓝堇碱等可以作用于HSP90AB1、PRKACA等靶点,通过抗炎、抗氧化应激等途径发挥治疗COPD的作用。 Objective To analyze the medication rules of Professor Li Jiansheng in treating chronic obstructive pulmonary disease(COPD)using data mining techniques,and to explore the potential mechanism of the screened core herbal combination against COPD using network pharmacology methods.Methods Effective medical records of COPD patients treated by Professor Li Jiansheng in outpatient clinics from November 2014 to March 2024 were collected.Frequency analysis,association rules analysis,and hierarchical clustering analysis were employed to analyze the medication patterns and to screen out the core herbal combination.Network pharmacology and molecular docking techniques were used to investigate the potential therapeutic mechanism of the core herbal combination against COPD.Results(1)A total of 375 prescriptions involving 179 distinct Chinese herbs were screened.The commonly used herbs by Professor Li for COPD included Ginseng Radix et Rhizoma,Poria,Pinelliae Rhizoma,Fritillariae Thunbergii Bulbus and Magnoliae Officinalis Cortex.The herbal properties were predominantly warm and cold;the flavors were mainly bitter,pungent,and sweet,with herbs primarily attributed to the lung,spleen,stomach,and kidney meridians.Association rules analysis yielded herb combinations such as Poria-Ginseng Radix et Rhizoma,Fritillariae Thunbergii Bulbus-Ginseng Radix et Rhizoma,Poria-Pinelliae Rhizoma-Ginseng Radix et Rhizoma.Hierarchical clustering analysis generated five herbal groupings,including Ginseng Radix et Rhizoma-Poria-Pinelliae Rhizoma-Fritillariae Thunbergii Bulbus-Magnoliae Officinalis Cortex,Citri Reticulatae Pericarpium-Perillae Fructus-Perillae Caulis-Farfarae Flos-Belamcandae Rhizoma-Asteris Radix et Rhizoma.The core herbal combination was screened as Ginseng Radix et Rhizoma-Poria-Pinelliae Rhizoma-Fritillariae Thunbergii Bulbus-Magnoliae Officinalis Cortex.(2)Network pharmacology identified 84 potential targets for the core herbal combination against COPD.The core targets included cellular tumor antigen p53(TP53),transcription factor Jun(JUN),tumor necrosis factor(TNF),RAC serine/threonine-protein kinaseα(AKT1),estrogen receptor(ESR1),transcription factor p65(RELA),protein kinase C alpha type(PRKACA),interleukin-1β(IL-1β),heat shock protein 90β(HSP90AB1),among ten key targets.The main active components includedβ-sitosterol,kaempferol,stigmasterol,among ten constituents.The mechanism of action of the core herbal combination against COPD was associated with signaling pathways such as lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,TNF signaling pathway,and chemical carcinogenesis-receptor activation.Molecular docking results indicated favorable binding activity between the core targets and the main active components.Conclusion Professor Li Jiansheng’s treatment of COPD is based on the main pathogenesis of“deficiency of healthy qi and accumulation of damage,”forming a characteristic therapeutic approach of“regulating and tonifying the lung and kidney,clearing and resolving,diffusing and descending”.The main active components of the core herbal combination(Ginseng Radix et Rhizoma-Poria-Pinelliae Rhizoma-Fritillariae Thunbergii Bulbus-Magnoliae Officinalis Cortex),such as baicalein and corydaline,may act on targets like HSP90AB1 and PRKACA,exerting therapeutic effects against COPD through pathways including anti-inflammation and anti-oxidative stress.

作者赵川冯贞贞李彬王明航 ZHAO Chuan;FENG Zhenzhen;LI Bin;WANG Minghang(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003 Henan,China;Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province&Education Ministry of P.R.China,Henan University of Chinese Medicine/Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Zhengzhou 450046 Henan,China)

机构地区河南中医药大学医学院河南中医药大学第一附属医院河南中医药大学呼吸疾病中医药防治省部共建协同创新中心/河南省中医药防治呼吸病重点实验室

出处《中药新药与临床药理》北大核心 2026年第2期343-354,共12页 Traditional Chinese Drug Research and Clinical Pharmacology

基金国家重点研发计划中医药现代化重点专项(2023YFC3502602) 全国名老中医药专家传承工作室建设项目(国中医药人教函〔2022〕75号) 河南省科技攻关项目(242102310558) 河南中医药大学科研苗圃工程项目(MP2024-05)。

关键词慢性阻塞性肺疾病数据挖掘网络药理学用药规律分子对接作用机制人参-茯苓-半夏-浙贝母-厚朴调补肺肾清化宣降抗炎抗氧化应激 chronic obstructive pulmonary disease data mining network pharmacology medication rules molecular docking mechanism of action Ginseng Radix et Rhizoma-Poria-Pinelliae Rhizoma-Fritillariae Thunbergii Bulbus-Magnoliae Officinalis Cortex regulating and tonifying the lung and kidney clearing and resolving,diffusing and descending anti-inflammation anti-oxidative stress