张云 杨卉 何轩辉 吴广均 李军

摘要 目的：用網络药理学方法探讨麻杏石甘汤成分、靶点、通路和生物学功能，阐明其治疗新型冠状病毒肺炎（COVID-19）细胞因子风暴的作用机制。方法：通过TCMSP、TCMID数据库以及文献报道，搜索麻杏石甘汤每味中药的成分和靶点，用Cytoscape软件构建和成分-靶点网络。用STRING搜素靶点的相关蛋白，并构建PPI网络。利用MECODE和ClusterOne聚类找出二者共同的关键靶点。利用Metascape和ClueGO对关键靶点进行通路和生物学功能富集分析。结果：麻杏石甘汤中麻黄有效成分6个、苦杏仁8个、石膏3个、生甘草92个。聚类分析得到67个关键靶点，其中IL-6和TNF是重要的核心靶点。麻杏石甘汤主要参与的分子通路和生物学功能与病毒感染和细胞因子免疫调节相关的是：人T细胞白血病病毒1型（TLV-1）感染;单纯疱疹病毒感染;TNF-R1信号通路和相关信号复合物;整合素1途径;白细胞介素信号;TH17细胞分化;炎性反应的调节;PI3K-Akt信号通路;白细胞介素-2介导的信号通路;免疫应答中细胞因子分泌的负调控;内皮屏障建立的调控;T细胞稳态增殖的调控。结论：麻杏石甘汤通过多成分、多靶点对机体的病毒感染和免疫炎性反应起到多方面的调控，包括促进TH细胞分化和T细胞稳态抑制病毒复制，负调控白细胞介素、TNF、整合素等免疫炎性反应递质消除细胞因子风暴。麻杏石甘汤针对COVID-19的病毒复制和细胞因子风暴具有显著的调节作用。

关键词 麻杏石甘汤;新型冠状病毒肺炎;细胞因子风暴;网络药理学

Abstract Objective：To discuss the composition， targets， pathways and biological functions of Maxing Shigan decoction and explore its curative mechanism of on COVID-19 cytokine storm by using network pharmacology. Methods：The components and targets of each Chinese herbal medicine of Maxing Shigan Decoction were searched through TCMSP and TCMID database， and literatures. The component target network was constructed by using the Cytoscape software. The PPI network was constructed by searching the protein related to the target in STRING database. MECODE and ClusterOne clustering software were used to find the common key targets. Metascape and ClueGo software were used to analyze the pathway and biological function enrichment of key targets. Results：In Maxing Shigan decoction， ephedra has 6 effective components， bitter apricot seed 8， gypsum 3 and liquorice root 92. Among the 67 key targets obtained by cluster analysis， IL6 and TNF are important core targets. The main molecular pathways and biological functions of Maxing Shigan decoction related to virus infection and cytokine immunoregulation are：HTLV-1 （human T-cell leukemia virus type 1） infection; herpes simplex virus infection; TNF-R1 signal pathway and related signal complexes; integrin 1 pathway; interleukin signal; Th17 cell differentiation; regulation of inflammatory response; PI3K Akt signaling pathway; interleukin-2-mediated signaling pathway; negative regulation of cytokine secretion in immune response; regulation of endothelial barrier establishment; regulation of T cell homeostatic proliferation. Conclusion：Based on network pharmacology， Maxing Shigan decoction can regulate virus infection and immune inflammatory response in many aspects through multi-component and multi-target， including promoting TH cell differentiation and T cell homeostatic proliferation to inhibit virus proliferation， and negatively regulating immune inflammatory factors such as interleukin， TNF， integrin to eliminate cytokine storm. Maxingshigan decoction has a significant regulatory effects on COVID-19 virus replication and cytokine storm. This study clarified the mechanism of the treatment of new coronary pneumonia with Lianhuang Qingwen， Jinhua Qinggan， Qingfei Paidu decoction and other prescriptions based on Maxing Shigan from one aspect， and provided a scientific basis for clinical rational drug use.

Keywords Maxingshigan Decoction; COVID-19; Cytokine storm; Network pharmacology

中图分类号：R289.4文献标识码：Adoi：10.3969/j.issn.1673-7202.2020.13.011