基于网络药理学和分子对接技术对灯盏细辛治疗糖尿病视网膜病变的分子机制的研究

Study on the molecular mechanism of erigeron breviscapus on the treatment of diabetic retinopathy based on network pharmacology and molecular docking

目的利用网络药理学研究方法寻找灯盏细辛有效成分治疗DR潜在分子机制,并通过分子对接技术验证主要有效成分与DR相关靶蛋白的有效结合能力。方法利用TCMSP数据库获得灯盏细辛有效成分和靶点蛋白。并利用GeneCards、OMIM和GEO数据库获得DR相关基因,取得药物-疾病共同靶点蛋白。通过Cytoscape 3.7.2软件构建中药活性成分-靶点蛋白-疾病网络图、STRING平台构建PPI网络图。利用R语言对药物-疾病共同靶点进行GO富集分析和KEGG富集分析;根据分析结果选取关键靶点蛋白和有效成分分子;并在RCSB PDB数据库取得关键蛋白结构、TCMSP获取有效成分分子结构,使用AutoDock Vin软件对有效成分和靶点蛋白进行分子对接验证。结果通过上述方法共筛选得到DR相关基因共7034个,中药有效成分12个及靶点基因176个,其中药物-疾病共同靶点121个,涉及有效成分9个;GO富集分析提示灯盏细辛涉及P<0.05的生物过程共2341条;KEGG富集分析显示P<0.05的通路共166条;灯盏细辛关键有效成分黄芩素(baicalein)、槲皮素(quercetin)及木犀草素(luteolin)能与与相应靶点蛋白VEGF、HIF1-α和p53能形成有效的分子结合。结论通过网络药理学研究方法发现灯盏细辛可以通过其多种有效成分的多靶点、多通路的共同作用治疗DR,并,并且通过分子对接技术验证了其有效成分可以与相应的DR相关靶蛋白形成有效的结合,为进一步实验提供了基础。

Objective To find out the potential mechanism of active components of Erigeron Breviscapus on the treatment of Diabetic Retinopathy(DR)via the Network Pharmacology and Molecular Docking.Methods The active components and targets of Erigeron Breviscapus were obtained from TCMSP database,and the genetic information of common targets were obtained from the GeneCards,OMIM and GEO databases.Cytoscape software(version 3.7.2)was used to construct the network diagram of active components-targets-disease,and PPI network diagram were constructed by STRING platform.GO enrichment analysis and KEGG enrichment analysis of common targets were performed by R(version 3.6.0).Autodock vina software(version 1.1.2)was used to virtually simulate possible combination modes between active components of Erigeron Breviscapus and key targets in DR obtained from TCMSP and RCSB PDB databases respectively.Results A total of 7034 DR-related genes,12 active components and 176 target genes were obtained through the above-mentioned methods.Among them,121 common drug-disease targets and 9 active components were involved.GO enrichment analysis and KEGG enrichment analysis shows that the therapeutic effect of QDMM Capsule on DR involves 2341 biological processes and 166 pathways with P<0.05.The potent active components ranked by degree value of network include baicalein,luteolin and quercetin;According to the docking results of these components with key targets of VEGF,HIF1-αand p53,the active components of Erigeron Breviscapus could form stable combination modes with key targets of DR.Conclusion We found that the Erigeron Breviscapus could treat DR through multi-targets and multi-pathways joint effects of its various active components by network pharmacology methods,and we also verified that the active components of Erigeron Breviscapus can form stable bond with key targets of DR through molecular docking verification.