基于网络药理及分子对接技术探讨固本平喘药物治疗慢性阻塞性肺疾病稳定期的作用机制

刘迪; 窦丹; 彭钰; 张洪春

doi:10.16025/j.1674-1307.2023.08.021

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基于网络药理及分子对接技术探讨固本平喘药物治疗慢性阻塞性肺疾病稳定期的作用机制

临证纵横 | 更新时间：2023-09-18

- 基于网络药理及分子对接技术探讨固本平喘药物治疗慢性阻塞性肺疾病稳定期的作用机制
- Exploration of mechanism of GubenPingchuan drugs in the treatment of chronic obstructive pulmonary disease in stable phase based on network pharmacology and molecular docking technology
- 北京中医药 2023年42卷第8期页码：897-906
- 作者机构：
  
  1.北京中医药大学,北京 100029
  2.首都医科大学附属北京中医医院消化科,北京 100029
  3.中日友好医院呼吸中心中医肺病科,北京 100029
- 作者简介：
  
  刘迪，女，29岁，博士研究生，住院医师。研究方向：中医肺系病临床与基础研究。
  张洪春，E-mail： 13701226664@139.com
- 基金信息：
  
  国家自然科学基金资助项目(82074367);国家中医药管理局中医药传承与创新“百千万”人才工程（岐黄工程）项目(2019-QTL-003)
- DOI：10.16025/j.1674-1307.2023.08.021
  中图分类号：
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刘迪，窦丹，彭钰，等.基于网络药理及分子对接技术探讨固本平喘药物治疗慢性阻塞性肺疾病稳定期的作用机制［J］.北京中医药，2023，42（8）：897-906.

LIU Di,DOU Dan,PENG Yu,et al.Exploration of mechanism of GubenPingchuan drugs in the treatment of chronic obstructive pulmonary disease in stable phase based on network pharmacology and molecular docking technology[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):897-906.
刘迪，窦丹，彭钰，等.基于网络药理及分子对接技术探讨固本平喘药物治疗慢性阻塞性肺疾病稳定期的作用机制［J］.北京中医药，2023，42（8）：897-906. DOI： 10.16025/j.1674-1307.2023.08.021.

LIU Di,DOU Dan,PENG Yu,et al.Exploration of mechanism of GubenPingchuan drugs in the treatment of chronic obstructive pulmonary disease in stable phase based on network pharmacology and molecular docking technology[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):897-906. DOI： 10.16025/j.1674-1307.2023.08.021.

摘要

目的,2,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,2,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,2,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,2,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。

Abstract

Objective,2,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,2,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-targets-disease" 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,2,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-1β had good docking effect. Gene expression profile data showed that IL-1β and 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,2,Professor ZHANG Hong-chun's Guben Pingchuan drugs for COPD patients in stable stage containquercetin， β-sitosterol and other components in core drugs act on IL， AKT1 and other targets， and play a role in the immune， inflammatory response， oxidative stress and other processes of COPD patients by regulating IL-17， TNF and other signal pathways.

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

Keywords

Chronic obstructive pulmonary diseasestationary phaseGubenPingchuan drugsempirical prescriptionnetwork pharmacologymolecular mechanismtherapeutic targets

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