摘要
目的:通过网络药理学与分子对接方法探究严长宏教授治疗新型冠状病毒感染的核心处方的分子机制和作用靶点,为后续临床治疗提供依据。方法:收集严长宏教授2022年底于包头市方舱医院的诊疗新型冠状病毒感染患者数据,构建疾病数据库,使用数据挖掘得出治疗核心处方。利用网络药理学的方法预测新型冠状病毒感染的靶点以及潜在通路,使用中药系统药理学数据库与分析平台(TCMSP)数据库筛选核心处方药物的有效成分以及靶点。通过人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、疗效药靶(TDD)数据库获取新型冠状病毒感染相关的靶点;取交集靶点后上传至STRING数据库构建蛋白质-蛋白质相互作用网络,导入Cytoscape 3.7.1软件中,运用Network analyzer插件得到核心靶点,并进行基因本体论(GO)以及京都基因与基因组百科全书(KEGG)富集分析。最后通过Autodock vina软件进行分子对接,对关键成分与靶点进行验证。结果:筛选出162个核心处方的有效成分,其中槲皮素、豆甾醇、山柰酚、谷甾醇、汉黄芩素等是关联度值最高的化合物。获得73个交集靶点,其中JUN原癌基因(Jun Proto-Oncogene,JUN)、信号转导因子和转录激活因子(Signal Transducer and Activator of Transcription,STAT)3、RELA癌基因(RELA Proto-Oncogene,RELA)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6等为关联成分最多的靶点基因。GO与KEGG富集分析结果显示核心处方治疗新型冠状病毒感染的通路有IL-17信号通路、TNF信号通路以及T细胞受体(T Cell Receptor,TCR)通路等。分子对接结果显示核心处方中的槲皮素、汉黄芩素、山柰酚等与多个关键的核心靶点通过氢键结合。结论:研究初步阐释了严长宏教授的核心处方治疗新型冠状病毒感染的作用机制,体现了中药治疗新型冠状病毒感染多药物、多通路、多信号的优势,以期为后续临床治疗提供理论依据。
Objective:To explore the molecular mechanism and targets of Professor YAN Changhong’s core prescription for the treatment of COVID-19 through network pharmacology and molecular docking methods,so as to provide a basis for subsequent clinical treatment.Methods:The data of Professor YAN Changhong’s diagnosis and treatment of patients infected with COVID-19 at the end of 2022 in Baotou Fangcang Hospital were collected,the disease database was constructed,and the core prescriptions for treatment were obtained by data mining.The target and potential pathway of COVID-19 were predicted by network pharmacology,and the active ingredients and targets of core prescription drugs were screened by using TCMSP database.Obtain targets related to COVID-19 through GeneCards,OMIM,and TDD databases.After taking the intersection target,upload it to the STRING database to build a protein-protein interaction network,import it into Cytoscape 3.7.1 software,use the Network analyzer to obtain the core target,and perform GO and KEGG enrichment analysis.Finally,the molecular docking is carried out through Autodock vina software to verify the key components and targets.Results:The active ingredients of 162 core prescriptions were screened,among which quercetin,stigmasterol,kaempferol,sitosterol and baicalein were the compounds with the highest correlation value.A total of 73 intersection targets were obtained,among which JUN,STAT3,RELA,TNF,IL-6,etc.were the target genes with the most associated components.The results of GO and KEGG enrichment analysis showed that the core prescription pathway for the treatment of COVID-19 included IL-17 signaling pathway,TNF signaling pathway and TCR pathway,etc..The molecular docking results showed that quercetin,baicalein,kaempferol,etc.in the core prescription were bound to multiple key core targets through hydrogen bonding.Conclusion:This study preliminarily explains the mechanism of action of Professor YAN Changhong’s core prescription in the treatment of COVID-19,and reflects the advantages of TCM medicine in the treatment of COVID-19 with multiple drugs,multiple pathways and multiple signals,in order to provide a theoretical basis for subsequent clinical treatment.
出处
《中医临床研究》
2023年第32期7-14,共8页
Clinical Journal Of Chinese Medicine
