基于网络药理学和动物模型验证研究泻白散治疗新型冠状病毒肺炎的潜在作用  

Study on the Potential Role of Xiebai Powder in the Treatment of COVID-19 Based on Network Pharmacology and Animal Model Validation

作　　者：徐明远 郭晓瑞[3] 刘佳[3] 刘洋[3] 张晶[1] 唐中华[3] Xu Mingyuan;Guo Xiaorui;Liu Jia;Liu Yang;Zhang Jing;Tang Zhonghua(Clinical Medical College,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Heilongjiang Academy of Forestry,Harbin 150040,China;College of Chemistry,Chemical Engineering and Resource Utilization,Northeast Forestry University,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学临床医学院,哈尔滨150040 [2]黑龙江省林业科学院,哈尔滨150040 [3]东北林业大学化学化工与资源利用学院,哈尔滨150040

出　　处：《世界科学技术-中医药现代化》2022年第9期3394-3405,共12页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：东北林业大学中央高校基本科研业务费专项资金资助项目(2572020DY04):中药清肺排毒汤抗新冠肺炎主效物质确证及其机制研究,负责人:唐中华;国家科学技术部国家科技基础资源调查计划(2019FY100502):小兴安岭禁伐区天然林野生经济植物种质资源调查,负责人:徐明远;黑龙江省人力资源和社会保障厅黑龙江省博士后基金面上项目(LBH-Z20091):促进刺五加活性成分积累的内生真菌筛选及其代谢调控机制研究,负责人:徐明远

摘　　要：目的通过网络药理学和动物模型验证的方法逆向研究泻白散对新型冠状病毒肺炎(COVID-19)的潜在治疗作用。方法首先在中药系统药理数据库分析平台筛选泻白散的活性成分;然后使用STITCH和Swiss Target Prediction数据库筛选活性成分的作用靶点;再通过GeneCards、CTD和OMIM数据库筛选COVID-19的疾病靶点;将药物靶点与疾病靶点映射后筛选出交集靶点,再将交集靶点构建PPI网络与活性成分-共同靶点网络,并对其进行GO和KEGG富集分析。最后使用Autodock Vina对核心成分与关键靶点进行分子对接验证,并使用急性肺损伤大鼠模型对泻白散的免疫调节作用进行动物试验验证。结果泻白散的核心活性成分为槲皮素,山奈酚,柚皮苷和异鼠李素;其作用于COVID-19的潜核心作用靶点为IL-8、IL-10、MAPK3、MAPK8和TNF-α,候选靶点富集的通路包括TNF-α、Toll样受体和NOD样受体信号通路等免疫相关代谢途径;泻白散可降低急性肺损伤大鼠模型血中免疫蛋白IgA、IgM、IgG以及细胞因子IL-8、IL-10、MAPK3、MAPK8和TNF-α的含量。结论泻白散可能通过调控TNF信号通路、NOD样受体和Toll样受体等免疫信号通路来治疗COVID-19引起的免疫因子风暴。本研究结果为开发治疗新型冠状病毒肺炎的中药新药提供了新的思路和理论基础。Objective Study the potential therapeutic effect of Xiebai Powder on Novel Coronavirus Pneumonia(COVID-19)by means of network pharmacology and animal model validation.Methods firstly,the active ingredients of Xiebai powder were screened on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform;Then,STITCH and Swiss Target Prediction databases were used to screen the action targets of active ingredients;Then the disease targets of COVID-19 were screened by Genecards,CTD and OMIM databases;After mapping the drug target with the disease target,the intersection target was screened,and then the intersection target was constructed into PPI network and active ingredient common target network,which were enriched and analyzed by GO and KEGG.Finally,Autodock Vina was used to verify the molecular docking between the active ingredients and key targets,and the immunomodulatory effect of Xiebai powder was verified by animal experiment using the rat model of acute lung injury.Results the core active ingredients of Xiebai powder were quercetin,kaempferol,naringin and isorhamnetin;The potential core targets of COVID-19 are IL-8,IL-10,MAPK3,MAPK8 and TNF-α.The enrichment pathways of candidate targets include TNF-α,Toll like receptor and Nod like receptor signal pathway and other immune related metabolic pathway;Xiebai powder can reduce the contents of immune protein IgA,IgM,IgG and cytokines IL-8,IL-10,MAPK3,MAPK8 and TNF-αin the blood of rats with acute lung injury.Conclusion Xiebai powder may treat COVID-19-induced immune factor storm by regulating TNF signaling pathway,nod like receptor and Toll like receptor.The results of this study provide a new idea and theoretical basis for the development of new Chinese medicine for the treatment of COVID-19.

关 键 词：泻白散 新型冠状病毒肺炎 网络药理学 分子对接 潜在作用 

分 类 号：R285.5[医药卫生—中药学]