目的 研究小柴胡湯在治療新型冠狀病毒肺炎（COVID-19）邪熱郁肺、樞機(jī)不利證過程中的功效作用網(wǎng)絡(luò)及潛在機(jī)制，分析方劑中抗新型冠狀病毒（SARS-CoV-2）的活性成分。方法 首先查閱文獻(xiàn)分析COVID-19邪熱郁肺、樞機(jī)不利證與小柴胡湯適應(yīng)證的方證對(duì)應(yīng)關(guān)系，繼而運(yùn)用網(wǎng)絡(luò)藥理學(xué)技術(shù)Cytoscape 3.6.0等軟件分別構(gòu)建小柴胡湯“中藥方劑-活性成分-關(guān)鍵靶點(diǎn)”功效作用網(wǎng)絡(luò)，并確認(rèn)方中抗SARS-CoV-2活性成分，從多方面分析小柴胡湯治療早期COVID-19邪熱郁肺、樞機(jī)不利證的功效作用及機(jī)制。結(jié)果 已有文獻(xiàn)報(bào)道中藥潛在抗SARS-CoV-2活性成分48個(gè)；共分析出小柴胡湯中治療肺炎、調(diào)節(jié)免疫的活性成分140個(gè)，其中黃芩素、芒柄花素、槲皮素等12個(gè)成分具有潛在抗SARS-CoV-2活性。小柴胡湯中活性成分通過IL-6、NOS2、ESR1等95個(gè)關(guān)鍵靶點(diǎn)進(jìn)行肺炎治療和免疫調(diào)節(jié)，涉及TNF信號(hào)通路、IL-17信號(hào)通路、甲型流感等多條通路?；蚬脖磉_(dá)和蛋白-蛋白互相作用（PPI）分析發(fā)現(xiàn)，血管緊張素轉(zhuǎn)化酶II（ACE2）僅與上述靶點(diǎn)中NOS2具有共表達(dá)，并且在PPI互作網(wǎng)絡(luò)中也僅與5個(gè)靶點(diǎn)有相互作用關(guān)系，推測ACE2靶點(diǎn)僅在SARS-CoV-2入侵人體的時(shí)候起到重要作用，而在病毒感染后的肺炎治療中作用甚微。結(jié)論 小柴胡湯中活性成分在抑制SARS-CoV-2活性、阻斷SARS-CoV-2入侵途徑、抑制炎癥風(fēng)暴、調(diào)節(jié)機(jī)體免疫等多方面發(fā)揮治療COVID-19的作用；值得注意的是針對(duì)ACE2靶點(diǎn)設(shè)計(jì)藥物可阻斷病毒入侵，但對(duì)肺泡內(nèi)炎癥等病變療效可能不佳，因此，這也為小柴胡湯對(duì)早期COVID-19治療提供了多靶點(diǎn)、多向性空間。另外，小柴胡湯用于治療早期COVID-19時(shí)尤應(yīng)注意精準(zhǔn)辨證用藥，一是避免產(chǎn)生不良反應(yīng)，二是避免加重COVID-19病情出現(xiàn)細(xì)胞因子損傷。

Objective To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of "Chinese medicine prescription-active ingredient-key target" for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.

R285.5

山東省重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2016ZDJS07A21）；山東省重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2017CXGC1301）；泰山學(xué)者工程專項(xiàng)經(jīng)費(fèi)項(xiàng)目（ts201511107）