基于方证对应探讨中药复方分期治疗新型冠状病毒肺炎的网络药理学机制

Network pharmacology mechanism of Chinese materia medicine compound in staging treatment of COVID-19 based on correspondence between prescription and syndrome

目的运用网络药理学的方法,以《新型冠状病毒感染的肺炎诊疗方案》第7版中的轻型(湿热蕴肺证)、普通型(湿毒郁肺证)、重型(气营两燔证)、危重型(内闭外脱证)和恢复期(气阴两虚证)5个证型及其对应复方为研究对象,分析探讨中医分期治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)过程中各证候及其所用复方的作用机制。方法通过检索中药系统药理学数据库和分析平台(TCMSP)等数据库和文献获取5个证型对应的复方的活性成分及其靶点,使用Geen Card等数据库检索5个证型临床表现的靶点,基于5个证型及其对应复方的活性成分的交集靶点建立蛋白互作(protein-protein interactions,PPI)网络,并进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。结果湿热蕴肺证、湿毒郁肺证、气营两燔证、内闭外脱证和气阴两虚证与其对应复方的活性成分的交集靶点数目分别是252、322、402、140和399,交集靶点主要包括VEGFA、EGFR、CASP3、AKT1等。5个证型对应复方干预的通路类型大体相似,但各复方干预通路的侧重点不同,湿热蕴肺证和湿毒郁肺证对应复方侧重于干扰病毒和增强机体的免疫应答;气营两燔证和内闭外脱证对应复方着重缓解神经系统的异常,以恢复机体神志;气阴两虚证对应复方进一步参与细胞生长过程和增强机体免疫功能,以扶助机体正气。结论5个证型对应复方以多成分、多靶点和多途径的方式,主要通过抗病毒、抑制炎症反应、增强免疫应答和保护主要靶器官来治疗COVID-19,这说明了中医辨证论治和方证对应的治疗特点,解释了中医分期治疗COVID-19的合理性。

Objective Taking the five syndromes of light(syndromes of damp and heat stagnating lung),normal(syndrome of dampness-toxicity stagnating lung),severe(syndrome of flaring heat in qi and ying),critical(syndrome of inner blocking causing collapse),and recovery(syndrome of qi-yin deficiency)period and their corresponding compounds in the seventh edition of Diagnosis and Treatment of COVID-19 as the research object,the mechanisms of various syndromes and compounds used in the stage treatment of COVID-19 by traditional Chinese medicine(TCM)was analyzed by using the method of network pharmacology.Methods The active components and their targets of five syndromes corresponding compounds were obtained from databases and literatures such as TCMSP,the targets of the five syndrome manifestations were retrieved using databases such as Gene Card.The protein-protein interaction(PPI)networks and KEGG pathway enrichment analysis were constructed based on the intersection targets of five syndromes and active components of their corresponding compounds.Results The intersection targets numbers of the syndromes of damp and heat stagnating lung,syndrome of dampness-toxicity stagnating lung,syndrome of flaring heat in qi and ying,syndrome of inner blocking causing collapse,and syndrome of qi-yin deficiency and their the active ingredients of the corresponding compounds were 252,322,402,140,and 399,respectively,and the intersection targets mainly included VEGFA,EGFR,CASP3,AKT1 and so on.The types of pathways for the five compounds interventions were generally similar,but the emphases of each compound intervention pathway were different.Syndromes of damp and heat stagnating lung and syndrome of dampness-toxicity stagnating lung corresponding compounds focused on interfering with the virus and enhancing the body’s immune response.Syndrome of flaring heat in qi and ying and syndrome of inner blocking causing collapse corresponding compounds focused on alleviating abnormalities of the nervous system to restore the body consciousness.Syndrome of qi-yin deficiency corresponding compounds further participated in the process of cell growth and enhanced the body’s immunity.Conclusion The five compounds treated COVID-19 through multiple components,multiple targets,and multiple pathways.The five compounds for the treatment of COVID-19 are mainly through anti-virus,suppression of inflammation,enhancement of immune response and protection of main target organs,which indicate the TCM characteristics of dialectical treatment and correspondence between prescriptions and syndromes,and explained the rationality of TCM to treat COVID-19 by stages.