摘要
目的采用网络药理学方法分析张洪春治疗慢性阻塞性肺疾病(COPD)稳定期经验方的作用机制,并进行分子对接等验证。方法整理张洪春教授治疗COPD稳定期患者的经验方及核心药物,核心药物根据其功效统称为固本平喘药物。在中药和疾病数据库查找筛选固本平喘药物有效成分、作用靶点及COPD的疾病靶点,使用Cytoscape 3.7.2软件绘制“药物-化合物-靶点-疾病”网络,并对药物与疾病交集靶点进行蛋白质相互作用(PPI)网络、基因本体(GO)功能富集及京都基因与基因组百科全书(KEGG)通路富集分析,揭示药物作用靶点及通路。用GenCLiP3、SwissDock、高通量基因表达数据库(GEO)数据库、中国知网(CNKI)和PubMed数据库分别对结果进行文献计算机辅助、基因表达谱及临床试验验证。结果张洪春教授治疗COPD的固本平喘药物包括当归、太子参、山茱萸、五味子、款冬花5味药物。共筛选出固本平喘药物相关的55种化学成分、182个靶点及COPD相关靶点647个,药物-疾病交集靶点93个。PPI网络分析示白细胞介素(IL)、丝氨酸/苏氨酸激酶1(AKT1)、血管内皮生长因子A(VEGFA)、基质金属蛋白酶(MMP)等靶点连接节点较多,GO、KEGG富集分析分别得到127个功能条目及141条信号通路。GenCLiP3平台对COPD易感基因网络分析及文献分析结果与网络药理学分析相符。分子对接显示槲皮素-AKT1、豆甾醇-IL-1β对接效果好。基因表达谱数据显示IL-1β、AKT1在COPD发病中发挥作用。CNKI和PubMed数据库也有多篇文献可以支撑本研究分析结果。结论张洪春教授治疗COPD稳定期患者固本平喘药物中含有槲皮素、β-谷甾醇等成分,作用于IL-17、AKT1等靶点,通过调节IL-17、肿瘤坏死因子(TNF)等信号通路在COPD患者免疫、炎症反应、氧化应激等过程中发挥作用。
Objective The mechanism of ZHANG Hong-chun′s experience in treating chronic obstructive pulmonary disease(COPD)in stable period was analyzed by network pharmacology,and the molecular docking was verified.Methods The empirical prescription and core drugs of Professor ZHANG Hong-chun in treating COPD patients in stable period were sorted out.The core drugs were collectively referred to as GubenPingchuan(stablizingthe root and soothing asthma)drugs according to their efficacy.The effective components,action targets and disease targets of Guben antiasthmatic drugswere searched and screenedin the database of traditional Chinese medicine and diseases.the software of Cytoscape 3.7.2 was usedto draw the"drugs-compounds-targetsdisease"network,and the PPI network,GO function enrichment and KEGG pathway enrichment of drug and disease intersection targets were analyzed to reveal the drug targets and pathways.GenCLiP3,SwissDock,GEO database,CNKI database and PubMed database were used to verify the resultsby literature computer-aided analysis,gene expression profiles and clinical trials.Results The GubenPingchuan drugs include Licorice,Angelicae Sinensis Radix,Pseudostellariae Radix,Farfarae Flos,Cornus Officinalis Sieb Et Zucc.A total of 55 chemical components,182 targets,647 COPD related targets and 93 drug disease intersection targets were screened.PPI network analysis showed that ILs,AKT1,VEGFA,MMPs and other target junction nodes were more than others.GO and KEGG enrichment analysis obtained 127 functional items and 141 signal pathways respectively.The results of GenCLiP3 platform′s network analysis and literature analysis were consistent with the network pharmacologic analysis.Molecular docking showed that quercetin-AKT1 and stigmasterol-IL-1βhad good docking effect.Gene expression profile data showed that IL-1βand AKT1 played a role in the pathogenesis of COPD.There were also many documents in CNKI and PubMed databases to support the analysis results of this study.Conclusion Professor ZHANG Hong-chun′s Guben Pin
作者
刘迪
窦丹
彭钰
张洪春
LIU Di;DOU Dan;PENG Yu;ZHANG Hong-chun(Beijing University of Chinese Medicine,Beijing 100029,China;Department of Digestion,Beijing Hospital of Traditional Chinese Medicine Affiliated to the Capital Medical University,Beijing 100029;Department of Traditional Chinese Medicine for Pulmonary Diseases,Center of Respiratory Medicine,China-Japan Friendship Hospital,Beijing 100029)
出处
《北京中医药》
2023年第8期897-906,共10页
Beijing Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(82074367)
中医药传承与创新“百千万”人才工程(岐黄工程)项目(2019-QTL-003)。
关键词
慢性阻塞性肺疾病
稳定期
固本平喘药物
经验方
网络药理学
分子机制
治疗靶点
Chronic obstructive pulmonary disease
stationary phase
GubenPingchuan drugs
empirical prescription
network pharmacology
molecular mechanism
therapeutic targets
