目的 基于数据挖掘分析《伤寒论》疫病治疗相关方剂的用药规律，并利用网络药理学分析核心药对“柴胡-黄芩”治疗新型冠状病毒肺炎(coronavirus disease 2019，COVID-19)的作用机制。以期探讨经方治疗疫病的当代价值。方法 筛选《伤寒论》中治疗疫病的经方，利用R语言等软件对频次、性味归经、相关性、关联规则等用药规律进行分析，并运用网络药理学方法对用药规律中核心药对治疗COVID-19的机制进行探究。用Cytoscape对筛选出的成分及靶点构建“疾病-药物-成分-靶点”网络，将关键靶点导入String数据库进行蛋白相互作用(protein-protein interaction，PPI)网络分析，并在R语言中进行基因本体论(gene ontology，GO)功能分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)通路分析。结果 纳入《伤寒论》中与疫病相关的方剂61首，共52味中药。前20味高频用药中以温性药、辛味药为主，多归脾、肺经，功效以补气药居多。“柴胡-黄芩”药对相关性最强，5个类聚方为小柴胡汤加减、四逆汤、麻杏石甘汤加减、茯苓白术汤及大承气汤。利用TCMSP和Genecards等网站获取了“柴胡-黄芩”药对的45个活性成分、189个作用靶点以及COVID-19的543个靶点，产生交集靶点64个，网络分析结果显示核心药对防治COVID-19的主要成分可能为槲皮素、汉黄芩素、山柰酚、黄芩素、刺槐素等，核心靶点可能为VEGFA、TNF、IL-6、TP53、AKT1、CASP3、CXCL8、PTGS2等，通过GO和KEGG富集分析分别获得1871个相关条目及164条通路。结论 《伤寒论》中治疗疫病多选用辛温、归脾、补气之品，善用小柴胡汤加减、四逆汤、大承气汤等。研究发现核心药对“柴胡-黄芩”通过PTGS2、IL-6、TNF等多靶点在抗炎、免疫调节等方面防治COVID-19，《伤寒论》中疫病治疗的古方对于当今疫病的防治可能有重要的借鉴价值。

Objective To analyze the medication rules of related epidemic disease prescription in Treatise on Febrile Diseases based on data mining, and the mechanism of “Chaihu (Bupleuri Radix)-Huangqin (Scutellariae Radix)” as the core drugs in the treatment of coronavirus disease 2019 (COVID-19) by network pharmacology, in order to explore the contemporary value of classical prescriptions in the treatment of epidemic diseases. Methods The prescriptions for treating epidemic diseases in Treatise on Febrile Diseases were screened, and the medication rules such as drug frequency, flavor and meridian tropism as well as correlation, apriori algorithm were analyzed by using software such as R language. The mechanism of the core drugs in the medication pattern in the treatment of COVID-19 was explored by the network pharmacology. A “disease-drug-ingredient-target” network was constructed on the selected components and targets with Cytoscape. The key targets were introduced into String database for network analysis of protein-protein interaction (PPI), and gene ontology (GO) functional analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were conducted in R language. Results A total of 61 prescriptions for treating epidemic diseases in Treatise on Febrile Diseases were included, including 52 traditional Chinese medicines (TCMs). In the top 20 high-frequency drugs, warm drugs, spicy drugs and qi-tonifying drugs were mainly used, mostly in the spleen and lung meridian. Chaihu (Bupleuri Radix) and Huangqin (Scutellariae Radix) herb pair had the strongest correlation. A total of five clusters were excavated: supplemented formula of Xiaochaihu Decoction (小柴胡汤), Sini Decoction (四逆汤), supplemented formule of Maxing Shigan Decoction (麻杏石甘汤), Fuling Baizhu Decoction (茯苓白术汤) and Dachengqi Decoction (大承气汤). A total of 45 active ingredients, 189 action targets of Bupleuri Radix-Scutellariae Radix herb pair, and 543 targets of COVID-19 were obtained from TCMSP and Genecards, and 64 intersection targets were generated. The results of the network analysis showed that the main components of core drugs pair against COVID-19 may be quercetin, wogonin, kaempferol baicalein, acacetin etc., and the core targets may be VEGFA, TNF, IL-6, TP53, AKT1, CASP3, CXCL8, PTGS2, etc. A total of 1871 related entries and 164 pathways were obtained by GO and KEGG enrichment analysis, respectively. Conclusion In Treatise on Febrile Diseases, the treatment of epidemic diseases mainly chose pungent, warm, spleen-invigorating and qi-tonifying herbs, such as Xiaochaihu Decoction, Sini Decoction and Dachengqi Decoction, etc. It was found that Bupleuri Radix-Scutellariae Radix core herb pair prevent and treat COVID-19 through multi-target targets such as PTGS2, IL-6 and TNF. The ancient prescriptions for treating epidemic disease in Treatise on Febrile Diseases may have significant reference value for the prevention and treatment of new epidemic diseases today.

国家社会科学基金重点项目(19AZD018)；江苏省中药资源产业化过程协同创新中心重点项目(ZDXM-2022-09)