目的 探討兒童清咽解熱口服液治療上呼吸道感染的潛在機(jī)制。方法 分別從TCMSP和Swiss Target Prediction數(shù)據(jù)庫(kù)中提取兒童清咽解熱口服液組方藥物的潛在生物活性成分和相應(yīng)的靶點(diǎn)，疾病靶點(diǎn)從GeneCards數(shù)據(jù)庫(kù)中獲取。通過(guò)Cytoscape軟件構(gòu)建"中藥材-化合物-靶點(diǎn)"網(wǎng)絡(luò)，并通過(guò)STRING web平臺(tái)分析蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)。在DAVID平臺(tái)上進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）功能富集分析，利用Maestro軟件進(jìn)行分子對(duì)接。采用RAW264.7細(xì)胞進(jìn)行體外Western blottitng和免疫熒光實(shí)驗(yàn)驗(yàn)證。結(jié)果 共篩選兒童清咽解熱口服液組方藥材含有的41種有效化合物，177種成分和疾病的共同靶點(diǎn)。其中，黃芩苷、柴胡皂苷、槲皮素、魚腥草素等是重要的活性化合物。PI3K、Akt、EGFR、MAPK3、GRB2、PIK3R1等是關(guān)鍵靶點(diǎn)。PI3K/Akt信號(hào)通路、HIF-1信號(hào)通路和FOXO信號(hào)通路被認(rèn)為是3條重要的信號(hào)通路。相關(guān)成分、靶點(diǎn)和通路與抗炎、抗病毒和免疫調(diào)節(jié)有關(guān)。分子對(duì)接結(jié)果提示，篩選的12個(gè)關(guān)鍵靶點(diǎn)可與大多數(shù)主要活性化合物緊密結(jié)合。Western blotting和免疫熒光實(shí)驗(yàn)結(jié)果顯示，兒童清咽解熱口服液可以抑制PI3K和Akt的蛋白表達(dá)，與網(wǎng)絡(luò)藥理學(xué)的預(yù)測(cè)結(jié)果一致。結(jié)論 兒童清咽解熱口服液主要通過(guò)調(diào)節(jié)PI3K/Akt等信號(hào)通路發(fā)揮治療兒童急性上呼吸道感染的作用。

Objective To investigate the potential mechanism of Ertong Qingyan Jiere Oral Liquid (EQJOL) in the treatment of upper respiratory tract infection (URTI). Methods The active ingredients and their corresponding targets were extracted from the TCMSP and Swiss Target Prediction databases, respectively, and the disease targets were obtained from the GeneCards database. Then, Cytoscape software was used to construct the "Chinese medica-compound-target" network, and the protein-protein interaction(PPI) network was analyzed by STRING web platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis were performed on DAVID platform, and then molecular docking was performed using Maestro software. Finally, RAW264.7 cells were used for in vitro Western blotting and immunofluorescence verification. Results A total of 41 effective compounds and 177 common targets of drugs and diseases were found to be associated with URTI. Among them, baicalin, saikosaponin, quercetin and houttuynin are important active compounds. PI3K, Akt, EGFR, MAPK3, GRB2 and PIK3R1 are the key targets. PI3K/Akt signaling pathway, HIF-1 signaling pathway and FOXO signaling pathway are considered to be three important signaling pathways. Relevant components, targets and pathways are related to anti-inflammatory, antiviral and immune regulation. Molecular docking results suggested that these 12 key targets could bind tightly to most of the major active compounds. Western blotting and immunofluorescence results showed that EQJOL inhibited the expression of PI3K and Akt, which was consistent with the prediction of network pharmacology. Conclusions EQJOL has a therapeutic effect in children with acute URTI mainly by regulating the PI3K/Akt signaling pathway.

R285.5

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃項(xiàng)目（LHGJ20210283）