基于网络药理学探讨清咳平喘颗粒治疗急慢性支气管炎合并慢性阻塞性肺疾病的作用机制  

Mechanism of Qingke Pingchuan Granule in Treatment of Acute and Chronic Bronchitis Complicated with Chronic Obstructive Pulmonary Disease:An Exploration Based on Network Pharmacology

作　　者：王添全 曹俊岭 胡金涛 董凌燕 欧阳竞锋[4] 林美娇[3] WANG Tian-quan;CAO Jun-ling;HU Jin-tao;DONG Ling-yan;OUYANG Jing-feng;LIN Mei-jiao(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Beijing Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Major Diseases,Medical Laboratory Center,China Academy of Chinese Medicine Sciences,Beijing 100700,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学东方医院,北京100078 [3]北京中医药大学东直门医院,北京100700 [4]中国中医科学院医学实验中心中医药防治重大疾病北京市重点实验室,北京100700

出　　处：《中国实验方剂学杂志》2021年第18期160-168,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家中医药管理局全国中医药创新骨干人才培训项目(国中医药人教函2019-128号);国家自然科学基金项目(81803915)。

摘　　要：目的:通过网络药理学的方法探讨清咳平喘颗粒治疗急慢性支气管炎合并慢性阻塞性肺疾病的潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)对清咳平喘颗粒进行活性成分筛选以及作用靶点预测,运用Cytoscape 3.8构建药物成分-靶点网络;检索GeneCards,在线人类孟德尔遗传数据库(OMIM)以及DrugBank数据库获取疾病靶点;将靶点名输入到UniProt数据库进行标准化处理;通过韦恩图,得到清咳平喘颗粒治疗二病靶点;使用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络;使用MetaScape数据平台进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析;构建清咳平喘颗粒治疗急慢性支气管炎合并慢性阻塞性肺疾病活性成分-共同靶点-信号通路网络。并通过文献确认相关靶点的准确性。结果:共获得清咳平喘颗粒165个活性成分,374个相关靶点,疾病相关靶点512个,药物疾病共同靶点130个,其中核心治疗靶点14个。对14个核心靶点进行分析,其中GO富集分析共得生物过程390条,细胞组成9个,分子功能23个;KEGG通路分析共得到22条信号通路。结论:清咳平喘颗粒可能是通过调节血管内皮生长因子受体2(KDR),转化生长因子-β1(TGF-β1),基质金属蛋白酶组织抑制因子-1(TIMP-1),细胞质膜微囊蛋白1(CAV1),低氧诱导因子-1α(HIF-1α),白细胞介素-2(IL-2)等靶点,在体内主要与细胞质内的调控因子的合成与转运有关,参与传递的细胞因子主要通过控制细胞增殖凋亡等功能来改善病情。Objective: To explore the potential mechanism of Qingke Pingchuan granule in treating acute and chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD)by network pharmacology. Method: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was retrieved to collect the active components of Qingke Pingchuan granule and predict the action targets,followed by the construction of component-target network using Cytoscape 3.8. GeneCards,Online Mendelian Inheritance in Man(OMIM),and DrugBank were used to harvest disease targets,whose names were put into UniProt for standardization. The treatment targets of Qingke Pingchuan Granule against the two diseases were obtained based on Venn diagram,which were then imported into the STRING platform for constructing the protein-protein interaction(PPI) network. Following the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis based on MetaScape,the active component-common target-signaling pathway network of Qingke Pingchuan granule against acute and chronic bronchitis complicated with COPD was finally constructed. The accuracy of the target was confirmed by literature. Result: A total of 165 active components,374 related targets,512 disease-related targets,and 130 common targets were obtained. Among them,the 14 core therapeutic targets were further subjected to GO enrichment analysis,which yielded 390 biological processes,nine cell components,and 23 molecular functions.The KEGG pathway analysis revealed 22 signaling pathways. Conclusion: Qingke Pingchuan granule alleviates the diseases possibly by regulating such targets as vascular endothelial growth factor receptor 2(KDR),transforming growth factor beta-1(TGF-β1),caveolin 1(CAV1),hypoxia-inducible factor-1 alpha(HIF-1α),and interleukin-2(IL-2),affecting the synthesis and transport of regulatory factors in cytoplasm,and controlling the cell proliferation and apoptosis.

关 键 词：清咳平喘颗粒 网络药理学 急慢性支气管炎 慢性阻塞性肺疾病 

分 类 号：R284.2[医药卫生—中药学] R289[医药卫生—中医学]