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基于网络药理学和实验验证探讨麦门冬汤治疗特发性肺纤维化的作用机制OA北大核心CSTPCD

Mechanism of Maimendong decoction in treating idiopathic pulmonary fibrosis based on network pharmacology and experimental validation

中文摘要英文摘要

目的:利用网络药理学方法并结合实验研究,深入探究麦门冬汤对特发性肺纤维化的治疗作用及其机制.方法:采用中药系统药理学数据库TCMSP、中国传统医学百科全书ETCM和SwissADME筛选并确定麦门冬汤中的活性成分.接着利用PubChem、SwissTargetPrediction和Uniport数据库挑选出中药活性成分的潜在作用靶标.借助GeneCards和OMIM数据库获取特发性肺纤维化的靶点基因.Venn diagrams绘图工具筛选出中药与疾病的交集靶点,利用Cytoscape3.9.1软件构建"中药-活性成分-疾病-靶点"网络关系图,并通过CytoNCA插件构建蛋白质相互作用网络,筛选得到核心靶点蛋白.运用DAVID进行GO及KEGG通路富集分析.最后使用博来霉素建立SD大鼠肺纤维化模型,观察大鼠肺组织肉眼标本及病理切片,并对其进行实时荧光定量PCR分析,比较治疗组与对照组TGF-β1、α-SMA、IL-4、IFN-γ、LC3-Ⅱ、beclin1的mRNA表达水平.结果:本研究共筛选得到麦门冬汤治疗IPF的作用靶点402个,其中核心靶点50个,对应5种中药的159种有效成分.GO富集分析和KEGG富集分析涉及PI3K-AKT信号通路、MAPK信号通路等信号通路治疗特发性肺纤维化.动物实验结果显示,与模型对照组相比,麦门冬汤治疗组可显著下调TGF-β1、α-SMA、IL-4 mRNA的相对表达水平(P<0.05),显著上调LC3-Ⅱ、beclin1、IFN-γ mRNA的相对表达水平(P<0.05).结论:本研究提示,麦门冬汤中关键活性成分可能在细胞自噬、炎症反应、巨噬细胞极化等生物过程方面发挥作用,发挥改善肺纤维化的作用.

Objective:To investigate the therapeutic effect and mechanism of Maimendong decoction on idiopathic pulmonary fibrosis by utilizing network pharmacology methods and combining experimental research.Methods:TCMSP,ETCM and Swiss ADME were used to screen the active ingredients of Maimendong decoction.Through PubChem,SwissTargetPrediction and Uni-port databases,the action targets of various components of traditional Chinese medicine were screened.The GeneCards database and OMIN database were applied to obtain target genes of idiopathic pulmonary fibrosis.Venn diagrams drawing tool was used to screen the intersection targets of traditional Chinese medicine and diseases.The"traditional Chinese medicine active ingredient dis-ease target"network diagram was constructed by using the Cytoscape 3.9.1 software,and the protein interaction network(PPI)was constructed by using the CytoNCA plug-in to screen the core target proteins.DAVID was used for enrichment analysis of GO and KEGG pathways.Finally,we used bleomycin to establish a pulmonary fibrosis model in SD rats,observed the macroscopic specimens and pathological sections of rat lung tissue,and conducted real-time fluorescence quantitative PCR analysis to compare the mRNA expression levels of TGF-β1,α-SMA,IL-4,IFN-γ,LC3-Ⅱ,and beclin1 between the treatment group and the con-trol group.Results:A total of 402 therapeutic targets of Maimendong decoction for IPF were screened,including 50 core targets,corresponding to 159 active ingredients of 5 traditional Chinese medicines.GO enrichment analysis and KEGG enrichment analysis involved the PI3K-AKT signal pathway,MAPK signal pathway and other signal pathways to treat idiopathic pulmonary fibrosis.The animal experiment results showed that compared with the model group,the Maimendong decoction group could significantly reduce the relative expression level of TGF-β1,α-SMA and IL-4 mRNA(P<0.05),significantly upregulated the relative expres-sion level of mRNA LC3-Ⅱ,beclin1,IFN-γ(P<0.05).Conclusion:This study suggests that the key active components of Mai-mendong decoction may play a role in biological processes such as autophagy,inflammatory reaction,macrophage polarization,and improve pulmonary fibrosis.

马先;于明玥;周博文;李泽峰;李传慧;辛玲杰;贾新华

山东中医药大学中医学院,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014山东大学附属公共卫生临床中心/山东省公共卫生临床中心中西医结合科,山东 济南 250013山东中医药大学附属医院呼吸与危重症医学科,山东 济南 250014

中医学

麦门冬汤特发性肺纤维化网络药理学实验验证自噬

Maimendong tangIdiopathic pulmonary fibrosisNetwork pharmacologyExperiment validationAutophagy

《海南医学院学报》 2024 (008)

597-606 / 10

This study was supported by Qilu Hygiene and Health Leading Talent Cultivation Project[Luwei Talent Zi(2020)No.3];Shandong Provincial Natural Science Foundation General Project(ZR2020MH353);2022 Youth Qihuang Scholar Training Program[Guozhong Pharmaceutical Education Letter(2022)No.256];Shandong Province Traditional Chinese Medicine High Level Talent Cultivation Project[Lu Wei Han(2023)No.143] 齐鲁卫生与健康领军人才培育工程[鲁卫人才字(2020)3号];山东省自然科学基金面上项目(ZR2020MH353);2022年青年岐黄学者培养项目[国中医药人教函(2022)256号];山东省中医药高层次人才培育项目[鲁卫函(2023)143号]

10.13210/j.cnki.jhmu.20231129.002

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