基于机器学习与网络药理学探究补阳还五汤治疗缺血性脑卒中的物质基础  

Integrated machine learning and network pharmacology approach for exploring the material basis of Buyang Huanwu Decoction for ischemic stroke

作　　者：王丰 孟庆琦 刘晴 刘影[3] 孙璐[3] 米妍 穆丹阳 何大阔[2] 侯悦 WANG Feng;MENG Qing-qi;LIU Qing;LIU Ying;SUN Lu;MI Yan;MU Dan-yang;HE Da-kuo;HOU Yue(College of Life and Health Sciences,Northeastern University,Key Laboratory of Bioresource Research and Development of Liaoning Province,National Frontiers Science Center for Industrial Intelligence and Systems Optimization,Shenyang I10170,China;College of Information Science and Engineering,State Key Laboratory of Synthetical Automation for Process Industries,Shenyang 110004,China;School of Pharmacy,Shenyang Pharmaceutical University,Benxi 117004,China)

机构地区：[1]东北大学生命科学与健康学院,辽宁省生物资源开发利用重点实验室,工业智能与系统优化国家级前沿科学中心,辽宁沈阳110170 [2]东北大学信息科学与工程学院,流程工业综合自动化国家重点实验室,辽宁沈阳110004 [3]沈阳药科大学药学院,辽宁本溪117004

出　　处：《药学学报》2025年第3期627-636,共10页Acta Pharmaceutica Sinica

基　　金：辽宁省重点实验室(2022JH13/10200026);中央高校基本科研业务费专项资金项目(N2220002)。

摘　　要：为了探究补阳还五汤(Buyang Huanwu Decoction,BHD)抗缺血性脑卒中(ischemic stroke,IS)药效作用及机制,本研究建立了大脑中动脉缺血再灌注(middle cerebral artery occlusion/reperfusion,MCAO/R)大鼠模型,初步评价了BHD在MCAO/R动物模型中的抗IS药效作用,然后将补阳还五汤的活性成分与FDA批准临床治疗IS的药物进行无监督聚类,并结合网络药理学预测活性成分的作用机制,最后建立脂多糖(lipopolysaccharide,LPS)诱导的BV-2细胞模型,采用Griess法和MTT法对BHD成分的抗炎活性及对细胞存活率的影响进行分析。结果显示,BHD能显著改善MCAO/R大鼠的神经功能评分,延长转棒停留时间,降低脑梗死体积及脑含水量,无监督聚类算法筛选得到BHD发挥药效的活性成分共7个,结合网络药理学预测分析活性成分的作用机制可能与炎症相关,使用LPS诱导BV-2细胞模型验证BHD活性成分的抗炎药效,并通过建立液相色谱-质谱联用法(LC-MS)考察不同活性成分在BHD中的含量。综上所述,本研究明确了补阳还五汤治疗IS的关键活性成分及其潜在的药效机制,对传统中药的现代化研究具有重要意义。所有动物实验均通过东北大学生物与医学伦理委员会审核批准(批准号:NEUEC-2023A052S)。The study investigates the therapeutic effects and mechanisms of Buyang Huanwu Decoction(BHD)in treating ischemic stroke(IS).Using a middle cerebral artery occlusion/reperfusion(MCAO/R)rat model,we evaluated the neuroprotective effects of BHD,demonstrating significant improvements in neurological function scores,prolonged rotarod retention time,and reductions in both infarct volume and brain water content.An unsupervised clustering algorithm was employed to identify active components of BHD by clustering them with FDA-approved drugs for ischemic stroke treatment.Combined with network pharmacology analysis,the mechanisms of these active components were predicted to be associated with anti-inflammatory pathways.Further validation using a lipopolysaccharide(LPS)-induced BV-2 cell model demonstrated the anti-inflammatory efficacy of seven key active components,with their effects on anti-inflammatory activity and cell viability assessed via the Griess and MTT assays.Additionally,the content of these active components in BHD was quantified using liquid chromatography-mass spectrometry(LC-MS).In conclusion,this study elucidates the critical active components of BHD and their potential pharmacological mechanisms,providing valuable insights for the modernization of traditional Chinese medicine and its application in ischemic stroke therapy.All animal experiments were approved by the Animal and Medical Ethics Committee of Northeastern University(approval No.:NEU-EC-2023A052S).

关 键 词：脑卒中 机器学习 网络药理学 补阳还五汤 无监督聚类 

分 类 号：R966[医药卫生—药理学]