摘要
目的基于网络药理学筛选通腑泻肺方治疗急性呼吸窘迫综合征(ARDS)的核心靶基因,并分析其可能的作用机制。方法通过中药系统药理学平台(TCMSP)数据库查找并筛选出通腑泻肺方的有效活性成分,从PubChem数据库等获得这些有效活性成分的简化线性分子输入规范(SMILES),从TCMSP数据库获取到有效活性成分的靶基因,并利用SwissTargetPrediction数据平台筛选有效活性成分的靶基因。通过DisGeNet、GeneCards和OMIM疾病数据库检索获得ARDS相关的疾病靶基因,并与通腑泻肺方有效活性成分的靶基因取交集,筛选得到通腑泻肺方与ARDS的潜在治疗靶基因。将潜在治疗靶点导入STRING12.0数据库,构建蛋白质相互作用(PPI)网络图,筛选得到通腑泻肺方治疗ARDS的核心靶基因。将通腑泻肺方有效活性成分和潜在治疗靶基因数据导入Cytoscape3.10.2软件,使用“Analyze Network”功能进行分析,选取Dgree值最大的前6种作为通腑泻肺方的核心有效活性成分。对核心靶基因进行GO功能、KEGG通路富集分析,采用分子对接技术观察核心有效活性成分与核心靶基因的分子结合能。结果筛选得到通腑泻肺方有效活性成分78种,其对应的靶基因729个;筛选得到ARDS相关疾病靶基因3207个;取交集后得到靶基因322个,作为通腑泻肺方与ARDS的潜在治疗靶基因,其中通腑泻肺方治疗ARDS的核心靶基因59个,包括白细胞介素6(IL-6)、蛋白激酶B(AKT1)、肿瘤坏死因子(TNF)等。筛选得到通腑泻肺方的核心有效活性成分为槲皮素、山奈酚、木犀草素、3′,4′,5,7-四甲氧基黄酮、异鼠李素、4′,5,7-三甲氧基黄酮等。GO功能及KEEG富集分析结果显示,通腑泻肺方治疗ARDS的核心靶基因在调控信号传导、酶活性和能量转移方面可能起到关键作用,主要作用于程序性死亡受体1(PD-L1)/程序性死亡配体1(PD-1)检查点通路、低氧诱导因子1(HIF-1)信号通路、Ras信号通路,PI3K-AKT信号通路等。分子对接结果显示,通腑泻肺方的核心有效活性成分与其对应的核心靶点蛋白均具有良好的结合能力。结论通腑泻肺方治疗ARDS的核心靶基因有IL-6、AKT1、TNF等,其机制与调控PD-L1/PD-1检查点通路、HIF-1信号通路、Ras信号通路、PI3K-AKT信号通路等有关。
Objective To identify the core target genes of Tongfu Xiefei formula in the treatment of acute respiratory distress syndrome(ARDS)using network pharmacology and to explore its potential mechanism of action.Methods The active ingredients of Tongfu Xiefei formula were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Simplified molecular input-line entry system(SMILES)data for these ingredients were obtained from databases such as PubChem.Target genes of the active ingredients were retrieved from the TCMSP database and were further screened using the SwissTargetPrediction platform.ARDS-related disease target genes were collected from the DisGeNet,GeneCards,and OMIM disease databases.The intersection of target genes from Tongfu Xiefei formula's active ingredients and ARDS-related genes was analyzed to select potential therapeutic target genes.These target genes were imported into the STRING 12.0 database to construct a protein-protein interaction(PPI)network,from which core target genes for ARDS treatment with Tongfu Xiefei formula were identified.Data for the active ingredients and potential therapeutic target genes were input into the Cytoscape 3.10.2 software.The"Analyze Network"function was used to study the network.The top six active ingredients with the highest Degree values were selected as the core ingredients of the formula.Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted on the core target genes,and molecular docking was used to assess the binding affinity between the core active ingredients and target genes.Results A total of 78 active ingredients of Tongfu Xiefei formula were identified,corresponding to 729 target genes.A total of 3,207 ARDS-related target genes were retrieved.The intersection analysis revealed 322 target genes,which were considered as potential therapeutic targets for ARDS treatment;59 core target genes were identified,including IL-6,AKT1,and tumor necrosis factor(TNF),etc.The core active ingredients of the formula identified for ARDS treatment were quercetin,kaempferol,luteolin,3′,4′,5,7-tetramethoxyflavone,isorhamnetin,and 4′,5,7-trimethoxyflavone.GO and KEGG pathway enrichment analyses indicated that the core target genes played a significant role in regulating signal transduction,enzyme activity,and energy transfer.These genes mainly affected pathways such as the PD-L1/PD-1 checkpoint pathway,HIF-1 signaling pathway,Ras signaling pathway,and PI3KAkt signaling pathway,etc.Molecular docking results demonstrated that the core active ingredients exhibited strong binding affinities with their corresponding target proteins.Conclusions The core target genes of Tongfu Xiefei formula for treatment of ARDS include IL-6,AKT1,and TNF,etc.The mechanism of action is related to the regulation of the PD-L1/PD-1 checkpoint pathway,HIF-1 signaling pathway,Ras signaling pathway,PI3K-Akt signaling pathway,and other related pathways.
作者
袁心叶
鲁俊
YUAN Xinye;LU Jun(The Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210001,China;不详)
出处
《山东医药》
2025年第3期7-11,共5页
Shandong Medical Journal
关键词
通腑泻肺方
急性呼吸窘迫综合征
网络药理学
分子对接
Tongfu Xiefei formula
acute respiratory distress syndrome
network pharmacology
molecular docking
