基于数据挖掘和网络药理学分析刘鑫教授治疗肺结节用药规律及作用机制

Medication patterns and mechanisms analysis of Professor Liu Xin in the treatment of pulmonary nodules based on data mining and network pharmacology

目的基于数据挖掘和网络药理学分析刘鑫教授治疗肺结节处方用药规律及核心药物组合作用机制。方法收集2020年1月至2022年1月就诊于南华大学附属第一医院中医科刘鑫教授门诊的肺结节患者198例处方,应用中医传承辅助平台(V 2.5)挖掘四气、五味、归经、核心药物组合、潜在新药物组合及新方等用药规律。采用网络药理学方法预测核心药物组合的有效成分、作用靶点和通路等作用机制。结果198例处方中涉及163味中药,药性以温、平、寒居多,药味以甘、辛、苦居多,归经以肺经、肝经、脾经和心经为主。高频药物组合为甘草-桔梗、甘草-石上柏等,核心药物为柴胡、生地黄、川牛膝、当归、红花、桃仁、赤芍、桔梗、枳壳、川芎、甘草、浙贝母、桑白皮、石见穿和石上柏,得到潜在新药物组合10个、新处方5个。网络药理学分析显示,核心药物组合治疗肺结节有效成分为槲皮素、山柰酚等,通过作用TP53、Akt1、JUN等靶点,调控AGE-RAGE、TNF、IL-17、HIF-1、PI3K-Akt、FoxO等信号通路起作用。结论刘鑫教授治疗肺结节以活血化瘀、疏肝理气、化痰散结和温肺化饮为主,兼以健脾益肾,体现其基于“龙虎回环”理论、“从肝论治”肺结节的学术特点,得出潜在新的药物组合及新方,为临床治疗肺结节提供新的思路,其核心药物组合治疗肺结节潜在靶点和作用机制主要参与炎症反应、血管生成、细胞增殖与凋亡等生物学过程,为进一步作用机制研究提供参考。

Objective To analyze prescription medication patterns and core drug combination mechanisms of Professor Liu Xin in the treatment of pulmonary nodules based on data mining and network pharmacology.Methods A total of 198 prescriptions of pulmonary nodule patients visited Professor Liu Xin’s Outpatient of Traditional Chinese Medicine Department at the First Affiliated Hospital of University of South China from January 2020 to January 2022 were collected.The medication patterns of four qi,five flavors,meridian tropism,core drug combinations,potential new drug combinations,and new prescriptions were explored by using traditional Chinese medicine inheritance assistance platform(V 2.5).The effective ingredients,targets,pathways,and other mechanisms of core drug combinations were predicted by using network pharmacology methods.Results Among 198 prescriptions,163 traditional Chinese medicines were involved,the majority of medicinal properties were warm,calm,and cold,the majority of medicinal flavors were sweet,spicy,and bitter,the main meridians were lung meridian,liver meridian,spleen meridian,and heart meridian.High-frequency drug combinations included Glycyrrhizae Radix Et Rhizoma-Platycodonis Radix,Glycyrrhizae Radix Et Rhizoma-Greater Selaginella,etc.The core drugs included Bupleuri Radix,Rehmanniae Radix,Cyathulae Radix,Angelicae Sinensis Radix,Carthami Flos,Persicae Semen,Paeoniae Radix Rubra,Platycodonis Radix,Aurantii Fructus,Chuanxiong Rhizoma,Glycyrrhizae Radix Et Rhizoma,Fritillariae Thunbergii Bulbus,Mori Cortex,Salvia Chinensis and Greater Selaginella,resulted in 10 potential new drug combinations and five new prescriptions.Network pharmacology analysis showed that the effective components of core drug combination in the treatment of pulmonary nodules were quercetin,kaempferol,etc.,which regulated AGE-RAGE,TNF,IL-17,HIF-1,PI3K-Akt,and FoxO signaling pathway by acting on TP53,Akt1 and JUN targets.Conclusion Professor Liu Xin in the treatment of pulmonary nodules mainly focuses on promoting blood circulation and removing blood stasis,soothing liver and regulating qi,resolving phlegm and dispersing nodules,and warming lungs and resolving yin,while also strengthening spleen and tonifying kidneys.This reflects his academic characteristics based on“dragon and tiger circle”theory and“treating from liver”pulmonary nodules,and proposes potential new drug combinations and prescriptions,providing new ideas for clinical treatment of pulmonary nodules.The potential targets and mechanisms of core drug combination therapy for pulmonary nodules mainly participate in biological processes such as inflammation,angiogenesis,cell proliferation and apoptosis,providing reference for further research on mechanisms of action.