摘要
目的研究新冠康复颗粒对于新型冠状病毒肺炎(COVID-19)瘥后肺纤维化的潜在保护机制。方法通过TCMSP、Uniprot数据库、中国药典获得新冠康复颗粒所含中药的性味归经、化学成分、作用靶点,获得靶蛋白基因,分析组成中药的成分信息,下载分子结构文件;通过GeneCards、OMIM数据库获取肺纤维化相关靶基因,将药物活性成分靶点与肺纤维化相关靶点相映射,获得新冠康复颗粒与肺纤维化作用相关的共有靶基因;运用Cytoscape3.7.0软件构建中药-成分-靶点网络;将共同作用靶点导入STRING平台进行蛋白互作分析;通过DAVID平台进行基因本体(GO)分析,基于京都基因与基因组百科全书(KEGG)通路富集分析,组织分布富集分析,运用R软件进行可视化;在RCSB PDB(RCSB Protein Data Bank)数据库下载VEGFR的晶体结构(PDB ID:2XIR)、FGFR的晶体结构(PDB ID:5EW8)晶体结构,借助AutoDock-Tool1.5.6、Vina软件,将受体与配体进行预处理及分子对接。结果新冠康复颗粒所含中药性味以"甘""寒"为主,归经主要在肺,其次在脾胃;经筛选新冠康复颗粒可作用于肺纤维化的中药活性成分有94种,相关作用靶基因133个。GO功能富集结果显示新冠康复颗粒主要涉及药物反应、转录调控、炎症反应、凋亡、氧化应激等生物学过程的调节;KEGG信号通路富集结果显示新冠康复颗粒主要涉及糖尿病并发症中的晚期糖基化终末产物及其受体(AGE-RAGE)信号通路、癌症信号通路、肿瘤坏死因子(TNF)信号通路、NF-κB信号通路等;组织富集结果显示新冠康复颗粒的中药成分主要富集在肺脏、肝脏、血液、成纤维细胞等组织;分子对接结果显示新冠康复颗粒前10位的活性化合物与VEGFR、FGFR的结合能均小于-6kcaL/mol。结论新冠康复颗粒可通过多种途径对COVID-19患者瘥后肺组织纤维化发挥保护作用。
Objective To explore the protecting mechanism of Xinguan-Kangfu Granules for treatment of pulmonary fibrosis caused by COVID-19.Methods Search through TCMSP,Uniprot databases and Chinese Pharmacopoeia to obtain the chemical constituents of TCM contained in Xinguan-Kangfu Granules,obtain the target protein gene,analyze the composition information of TCM,and download the molecular structure file.GeneCards,OMIM databases were used to search the target genes related to pulmonary fibrosis,obtain the common target genes of Xinguan-Kangfu Granules and pulmonary fibrosis.Cytoscape 3.7.0 was used to construct the TCM-component-target network.PPI network was obtained by using STRING database.The key targets were analyzed by Gene Ontology(GO),the Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment and tissue enrichment using David platform.The molecular docking was performed by AutoDock Tools 1.5.6 and Vina.Results Property and taste of Xinguan-Kangfu Granules are mainly cold and sweet.The meridian is mainly in the lung,followed by the spleen and stomach.There were 94 active components and 133 target genes associated with pulmonary fibrosis.The results of GO function enrichment analysis showed that Xinguan-Kangfu Granules mainly regulated the biological processes of drug response,transcriptional regulation,inflammatory response,apoptosis,and oxidative stress.KEGG pathway enrichment mainly involved AGE-RAGE signaling pathway in diabetic complications,pathways in cancer,TNF signaling pathway,NF-kB signaling pathway.The results of tissue enrichment showed that the key gene expression sites were mainly in lung,liver blood,fibroblasts.Molecular docking results showed that the binding energies of the top 10 active compounds of Xinguan-Kangfu Granules with VEGFR and FGFR were all less than-6 kcaL/mol.Conclusion Xinguan-Kangfu Granules may protect the pulmonary fibrosis of COVID-19 convalescent patients in multiple mechanisms.
作者
张思依
向阳
高清华
杨琼
段妍君
周燕萍
吕文亮
ZHANG Siyi;XIANG Yang;GAO Qinghua;YANG Qiong;DUAN Yanjun;ZHOU Yanping;LYU Wenliang(Hubei University of Chinese Medicine,Wuhan 430065)
出处
《湖北中医药大学学报》
2020年第5期16-21,共6页
Journal of Hubei University of Chinese Medicine
基金
国家重点研发计划项目(项目编号:2020YFC0845300)
作者简介
张思依(1991-),女,湖北中医药大学中医临床学院2018级博士研究生,研究方向:运用温病理论防治重大感染性疾病研究;通讯作者:吕文亮(1963-),男,湖北中医药大学教授,研究方向:温病治则的临床运用研究,脾胃湿热证量化标准研究,病证结合模式下运用疫病理论防治重大感染性疾病的研究,E-mail:lvwenliang66@126.com。
