网络药理学方法确定黄芪对咳嗽变异性哮喘的药理机制及临床疗效验证

Network pharmacology approach to determine the pharmacological mechanism of Astragalus on cough variant asthma and clinical efficacy validation

目的通过网络药理学方法研究黄芪治疗咳嗽变异性哮喘(CVA)的药理机制并进行临床疗效验证。方法利用TCMSP、UniProt数据库检索黄芪的主要化合物、对应的作用靶基因,通过GeneCards数据库获得CVA相关的疾病靶基因,将化合物靶基因与CVA相关的疾病靶基因取交集,得出黄芪治疗CVA的目标靶基因。利用Cytoscape3.6.0软件构建“中药-化合物-靶基因-疾病”网络,选出关键化合物,利用STRING数据库构建交集靶点基因蛋白相互作用网络(PPI),选出关键靶点。选取CVA患者80例,随机分为两组,治疗组加用黄芪治疗,比较疗效及诱导痰白细胞介素6(IL-6)水平。结果黄芪作用于CVA的有效化合物有15个,相关靶点62个,关键化合物为槲皮素、山奈酚、7-O-甲基异丙醇胺、芒柄花黄素、3,9-二-O-甲基尼森香碗豆紫檀酚等;关键靶基因为IL-6、胱天蛋白酶3(CASP3)、表皮生长因子受体(EGFR)等。治疗组临床治疗愈显率高于对照组(P<0.05),治疗后治疗组诱导痰IL-6水平低于对照组(P<0.05)。结论本研究通过网络药理学方法进行多层次网络分析,对黄芪治疗CVA多成分、多靶点的药理机制进行确定,实现分子作用的综合网络分析,从整体角度阐明黄芪治疗CVA的作用机制,IL-6是黄芪治疗CVA的主要靶点,临床研究验证显示黄芪治疗CVA降低诱导痰IL-6水平,临床疗效显著。

Objective To determine clinical efficacy validation and pharmacological mechanism of Astragalus in treating cough variant asthma(CVA)by network pharmacology.Methods The main compounds of Astragalus and the corresponding target genes were searched from TCMSP and UniProt database,the related target genes of CVA were obtained from GeneCards database.The compound target gene and CVA target gene were intersected to obtain the predictive target of astragalus in the treatment of CVA.The network of medicine,compound,target and disease was constructed by Cytoscape3.6.0 software and the key compounds were selected.The key target genes were selected by using STRING database to construct protein-protein interaction network(PPI).Eighty patients with CVA were randomly divided into two groups.The treatment group was treated with Astragalus.The curative effect and the level of interleukin 6(IL-6)in sputum were compared.Results There were 15 effective compounds and 62 related targets of Astragalus acting on CVA,the key compounds were quercetin,kaempferol,7-O-methylisomucronulatol,formononetin and 3,9-di-O-methylnissolin and so on.The key target genes were IL-6,caspase3(CASP3)and epithelial growth factor receptor(EGFR).Conclusion In this study,through the multi-level network,the mechanism of Astragalus in the treatment of CVA is clarified from the overall point of view.IL-6 is the main target of Astragalus in the treatment of CVA.Astragalus could reduce the level of IL-6 in sputum of CVA patients,and the clinical effect is remarkable.