基于网络药理学与分子对接的化肝煎对失眠、慢性萎缩性胃炎和胃食管反流病“异病同治”作用机制探讨  

Mechanism of Hua-Gan Decoction in treating insomnia, chronic atrophic gastritis and gastroesophageal reflux disease based on network pharmacology and molecular docking

作　　者：邓雅凤 王洋洋 鱼涛 DENG Yafeng;WANG Yangyang;YU Tao(Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;The First Department of Gastroenterology,Shaanxi Provincial Hospital of Chinese Medicine,Xi'an 710003,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]陕西省中医医院脾胃病一科,陕西西安710003

出　　处：《药物评价研究》2022年第11期2176-2187,共12页Drug Evaluation Research

基　　金：国家重点研发计划项目(2017YFC1700601);“十三五”国家重点研发计划中医药现代化研究专项(2017YFC1703703);陕西省特支计划科技创新领军人才项目(646)。

摘　　要：目的 以中医“异病同治”理论为依据,采用网络药理学与分子对接方法探讨化肝煎“异病同治”失眠、慢性萎缩性胃炎和胃食管反流病的作用靶点及可能作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)等中药化合物数据库结合文献挖掘获取化肝煎的化学成分和作用靶点;结合GeneCards、OMIM、PharmGKB、DRUGBANK、TTD数据库获取化肝煎治疗失眠、慢性萎缩性胃炎和胃食管反流病的作用靶点。采用Cytoscape软件绘制化肝煎中药-成分-靶点网络,利用Venny软件得出相关交集基因。基于Cytoscape软件绘制化肝煎-成分-靶点可视化网络图,借助STRING数据库及Cytoscape软件构建蛋白质相互作用(PPI)网络,分析获得核心作用靶点。采用Metascape平台工具对其进行基因本体论(GO)注释及京都基因与基因组百科全书(KEGG)通路富集分析。使用AutodockTools软件对化肝煎主要活性成分与疾病作用靶点进行分子对接。结果 筛选得到化肝煎化学成分56个,疾病靶点:失眠438个,慢性萎缩性胃炎868个,胃食管反流病4 252个,以及20个药物成分和疾病共同靶点。PPI网络中关键蛋白排名靠前的靶点为IL6、NCF1、PTGS2、CRP、MPO、PPARG、TNF等。获得GO富集分析结果排名靠前的有452种生物过程(BP)、19种分子功能(MF)、6种细胞组分(CC),KEGG信号通路主要有6条信号通路。分子对接结果显示关键成分与对应靶点具有较好的结合活性。结论化肝煎治疗失眠、慢性萎缩性胃炎和胃食管反流病可能涉及TNF、IL6、PTGS2、PPARG、CRP等为代表的核心靶点,其实现异病同治的作用可能与脂质信号通路调控炎症、细胞因子反应等有关。Objective Based on the theory of "treating the different diseases with the same therapy" in traditional Chinese medicine,network pharmacology and molecular docking method were used to explore the target and possible mechanism of Hua-Gan Decoction(HGD) "treating the different diseases with the same therapy" in insomnia, chronic atrophic gastritis and gastroesophageal reflux disease. Methods The chemical constituents and action targets of HGD were obtained by TCMSP and literature mining.Combined with GeneCards, OMIM, PharmGKB, DRUGBANK and TTD database, the therapeutic targets of HGD for insomnia,chronic atrophic gastritis and gastroesophageal reflux disease were obtained. Cytoscape software was used to draw the "TCMcomponent-target" network of gain, and the related intersection genes were obtained by Venny software. Based on Cytoscape software, a visual network map of "HGD-component-target" was drawn, and a PPI network was constructed with the help of STRING database and Cytoscape software to analyze and obtain the core targets. The Metascape platform tool was used for GO enrichment analysis and KEGG pathway analysis. AutodockTools were used to conduct molecular docking between the main active ingredients of HGD and the disease targets. Results A total of 56 chemical components of HGD, 438 disease targets of insomnia,868 chronic atrophic gastritis, 4 252 gastroesophageal reflux disease and 20 common targets of drug components and diseases were screened. The top targets of key proteins in PPI network were IL6, NCF1, PTGS2, CRP, MPO, PPARG, TNF, etc. GO enrichment analysis results were obtained for 452 biological processes, 19 molecular functions and six cellular components, and KEGG signaling pathways mainly included six signaling pathways. The molecular docking results showed that the key components had good binding activity with corresponding targets. Conclusion HGD may involve the core targets represented by TNF, IL6, PTGS2,PPARG and CRP in the treatment of insomnia, chronic atrophic gastritis and gastroesophage

关 键 词：化肝煎 失眠 慢性萎缩性胃炎 胃食管反流病 异病同治 网络药理学 

分 类 号：R285.5[医药卫生—中药学]