目的 從細(xì)胞因子角度，探究人參敗毒散多成分、多靶點(diǎn)、多途徑抗新型冠狀病毒肺炎（COVID-19）的作用機(jī)制。方法 應(yīng)用中藥系統(tǒng)藥理分析平臺(tái)（TCMSP）收集人參敗毒散中活性化合物，結(jié)合藥物靶點(diǎn)數(shù)據(jù)庫(kù)收集細(xì)胞因子風(fēng)暴相關(guān)靶點(diǎn)，利用Cytoscape構(gòu)建“藥材-化合物-疾病靶點(diǎn)”網(wǎng)絡(luò)。通過(guò)String和DAVID數(shù)據(jù)庫(kù)對(duì)靶點(diǎn)的互作網(wǎng)絡(luò)、GO功能和KEGG通路進(jìn)行分析。結(jié)果 人參敗毒散“藥材-活性化合物-疾病靶點(diǎn)”網(wǎng)絡(luò)包括10種藥材，211個(gè)活性成分和151個(gè)疾病靶點(diǎn)?；プ骶W(wǎng)絡(luò)發(fā)現(xiàn)人參敗毒散抑制細(xì)胞因子風(fēng)暴治療COVID-19的靶點(diǎn)可能包含STAT3、MAPK1、NFκB1、PIK3CA、MAPK3、TNF、CXCR4、VEGFA、IL-6、IL-2等。GO功能分析發(fā)現(xiàn)上述靶點(diǎn)在生物功能方面涉及趨化性、類固醇代謝過(guò)程等；在分子功能方面涉及血紅素結(jié)合、鐵離子結(jié)合、氧結(jié)合等；在細(xì)胞組成方面涉及細(xì)胞表面、細(xì)胞膜等。KEGG通路富集發(fā)現(xiàn)上述靶點(diǎn)參與查加斯病通路、HIF-1信號(hào)通路、腫瘤壞死因子信號(hào)通路等的調(diào)控。結(jié)論 人參敗毒散可能通過(guò)調(diào)節(jié)趨化性細(xì)胞因子，增加血氧飽和度，抑制STAT、MAPK、NFκB、PIK3K、IL-6等炎癥相關(guān)信號(hào)通路，實(shí)現(xiàn)多成分-多靶點(diǎn)-多途徑抑制細(xì)胞因子風(fēng)暴形成的抗COVID-19作用。

Objective To investigate the multi compound-target-pathway mechanism of Renshen Baidu Powder (RSBDS) in the treatment of COVID-19 from cytokine perspective. Methods The active compounds of RSBDS were collected by TCMSP and the cytokine storm related targets were collected by the drug target database. The interaction network of RSBDS on single drug-active compounds-targets was established by Cytoscape. The interaction network, GO function and KEGG pathway of the targets were analyzed by String and DAVID databases. Results The interaction network of RSBDS on single drug-active compounds-targets included 10 kinds of medicinal materials, 211 active compounds and 151 disease targets. Interaction network showed that the targets related to the inhibition to cytokine storm of RSBDS on COVID-19 might include STAT3, MAPK1, NFκB1, PIK3CA, MAPK3, TNF, CXCR4, VEGFA, IL-6, IL-2, etc. GO function showed that above targets in biological function involved chemotaxis and steroid metabolism; Molecular function entries involved heme binding, iron ion binding and oxygen binding; Cell composition entries involved cell surface and cell membrane. KEGG pathway showed that above targets participated in the regulation of Chagas disease, HIF-1 signaling pathway, TNF signaling pathway, etc. Conclusion The multi compound-target-pathways effect of RSBDS on COVID-19 was realized by inhibiting cytokine storm, which through regulating chemotaxis, increasing blood oxygen saturation, inhibiting STAT, MAPK, NFκB, PIK3K and IL-6 signal pathways.

R285.5

國(guó)家自然科學(xué)基金青年基金項(xiàng)目（81803508）