基于网络药理学的地龙平喘作用机制研究  

Mechanisms of Pheretima in Treatment of Asthma Based on Network Pharmacology

作　　者：马韫楠 吴娅丽 钟宛凌 汪文杰 杨万青[1] 张经纬 李鹏跃[1] 杜守颖[1] MA Yun-nan;WU Ya-li;ZHONG Wan-ling;WANG Wen-jie;YANG Wan-qing;ZHANG Jing-wei;LI Peng-yue;DU Shou-ying(Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学,北京102488

出　　处：《中国现代中药》2021年第10期1737-1746,共10页Modern Chinese Medicine

基　　金：北京市技术开发类横向课题(2017110031009877)。

摘　　要：目的:基于网络药理学方法研究地龙平喘的作用机制。方法:通过中国知网(CNKI)数据库、百链数据库、PubMed数据库文献检索和SwissADME平台筛选获得地龙活性化合物;通过SwissTargetPrediction预测活性成分的潜在靶点,并与OMIM、DrugBank数据库中哮喘的疾病靶点数据进行比对,获得地龙平喘的作用靶点;通过STRING 11.0平台分析靶点的蛋白质相互作用网络;通过Matascape数据库对地龙平喘靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析;采用Cytoscape 3.7.1软件构建成分-靶点-通路网络;通过豚鼠离体气管平滑肌诱导收缩实验验证地龙提取物对胆碱能受体兴奋引起的气管平滑肌收缩的抑制作用。结果:共收集地龙平喘活性成分56个,包括氨基酸、脂肪酸、核苷酸等,预测其作用靶点包括前列腺素G/H合酶2、毒蕈碱型乙酰胆碱受体家族、β2-肾上腺素受体等67个,潜在调控花生四烯酸代谢、胆碱能神经突触信号、色氨酸代谢等通路和生物过程。验证实验结果表明,地龙提取物对胆碱能受体兴奋引起的离体气管平滑肌收缩有明显的舒张作用。结论:地龙的平喘作用具有多成分、多靶点、多途径作用的特点,为地龙平喘作用机制的进一步研究提供了参考。Objective:To analyze the mechanism of Pheretima in treatment of asthma based on network pharmacology.Methods:The active components of Pheretima were retrieved from China National Knowledge Infrastructure(CNKI),MedaLink,and PubMed,and screened by SwissADME.The potential targets of the active components were predicted by SwissTargetPrediction and compared with the targets of asthma retrieved from OMIM and DrugBank.Thereby,the targets of Pheretima for treatment of asthma were screened out,followed by the construction of protein-protein interaction(PPI)network(STRING 11.0),Gene Ontology(GO)term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis(Metascape),and establishment of active component-target-pathway network(Cytoscape 3.7.1).The isolated tracheal spirals of guinea pig were used to test the inhibitory effect of Pheretima extract on the contraction of tracheal smooth muscle induced by M-receptor.Results:A total of 56 potential anti-asthmatic components of Pheretima were screened out,including amino acids,fatty acids,and nucleotides,and 67 targets were projected,such as beta-2 adrenergic receptor(ADRB2),muscarinic acetylcholine receptor(CHRM),and prostaglandin G/H synthase 2(PTGS2).These targets were mainly involved in the GO terms such as arachidonic acid metabolic process and KEGG pathways such as cholinergic synapse and tryptophan metabolism.The in vitro experiment verified the relaxant effect of Pheretima on the contracted tracheal smooth muscle induced by cholinergic receptor.Conclusion:This study reflects the multi-component,multi-target,and multi-pathway characteristics of Pheretima in the treatment of asthma,which provides clues for further research on the anti-asthmatic mechanism of Pheretima.

关 键 词：地龙 平喘 网络药理学 作用机制 

分 类 号：R285.5[医药卫生—中药学]