中药新药与临床药理2025，Vol.36Issue(12)：2091-2100,10.DOI:10.19378/j.issn.1003-9783.2025.12.009
基于网络药理学及生物信息学探讨四虫片治疗下肢动脉硬化闭塞症膝下病变的潜在作用机制
Exploring the Potential Mechanism of Sichong Tablets in Treating Below-the-Knee Lesions of Lower Extremity Arteriosclerosis Obliterans Based on Network Pharmacology and Bioinformatics
摘要
Abstract
Objective To investigate the potential mechanism of Sichong Tablets in treating below-the-knee lesions of lower extremity arteriosclerosis obliterans(LEASO)using network pharmacology and bioinformatics.Methods Active components and target genes of Sichong Tablets were retrieved and screened from databases including CNKI,PubMed,Coremine,and TCMSP.The GSE100927 dataset was downloaded from the GEO database to identify differentially expressed genes(DEGs)in BTK lesions.BTK-related genes were obtained by intersecting DEGs with gene modules identified through weighted gene co-expression network analysis(WGCNA).These were further intersected with target genes of Sichong Tablets to identify therapeutic targets.A drug-active component-disease-target gene network was constructed using Cytoscape 3.10.1.Four machine learning methods—least absolute shrinkage and selection operator(LASSO)regression,random forest(RF),support vector machine-recursive feature elimination(SVM-RFE),and Boruta algorithm—were applied to screen core genes.GO functional and KEGG pathway enrichment analyses were performed.Molecular docking between active components of Sichong Tablets and core genes was conducted using AutoDock Vina 1.2.3 to identify the conformation with the highest binding affinity.Results A total of 119 active components and 487 target genes of Sichong Tablets were identified.Among 295 DEGs in BTK lesions,211 were up-regulated and 84 were down-regulated.Intersection of DEGs and WGCNA modules yielded 210 BTK-related genes,which were further intersected with Sichong Tablets targets to obtain 9 therapeutic targets.Six core genes were identified through machine learning:PCDH12,COL1A1,CD68,PLCB2,CD36,and DPP4.These genes were significantly enriched in signaling pathways such as platelet activation,lipid and atherosclerosis,fat digestion and absorption,and cholesterol metabolism.PLCB2 exhibited lower binding energy with active components,while COL1A1,CD68,PLCB2,CD36,and DPP4 effectively bound to active components with good affinity.Conclusion Sichong Tablets may exert therapeutic effects on BTK lesions through active components such as Palmitate and Palmitic acid,acting on core targets including COL1A1 and PCDH12,and regulating key pathways like platelet activation and lipid and atherosclerosis.关键词
四虫片/下肢动脉硬化闭塞症/膝下病变/网络药理学/生物信息学/Palmitate/COL1A1/血小板活化通路/脂质与动脉粥样硬化通路Key words
Sichong Tablets/lower extremity arteriosclerosis obliterans/below-the-knee lesions/network pharmacology/bioinformatics/Palmitate/COL1A1/platelet activation pathway/lipid and atherosclerosis pathway分类
医药卫生引用本文复制引用
杨丽科,王华雨,王玉涛..基于网络药理学及生物信息学探讨四虫片治疗下肢动脉硬化闭塞症膝下病变的潜在作用机制[J].中药新药与临床药理,2025,36(12):2091-2100,10.基金项目
国家自然科学基金青年基金项目(82104860) （82104860）
山东省中医药科技发展计划项目(2019-0559) （2019-0559）
济南市卫生健康委员会科技计划项目(2019-1-23) （2019-1-23）
山东省医药卫生科技发展计划项目(2018WS478) （2018WS478）
济南市临床医学科技创新计划项目(202134013) （202134013）
济南市医疗卫生行业高层次人才专项经费资助项目(202412) （202412）
张红星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). （国中医药人教函[2022]75号）
