目的 研究桑菊飲治療急性肺損傷（ALI）的作用機(jī)制。方法 采用超高效液相色譜-電噴霧串聯(lián)四極桿飛行時(shí)間質(zhì)譜法（UHPLC-ESI-QTOF-MS/MS）快速鑒別桑菊飲的入血成分，使用 Swiss Target Prediction和 GeneCards等數(shù)據(jù)庫篩選桑菊飲入血成分關(guān)聯(lián)靶點(diǎn)與ALI相關(guān)靶點(diǎn)，并通過Venny確認(rèn)桑菊飲抗ALI潛在靶點(diǎn)。使用Metascape對交集靶點(diǎn)進(jìn)行基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析，通過String數(shù)據(jù)庫與Cytoscape軟件構(gòu)建并分析蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)?；诜肿訉訉χ匾煞趾桶悬c(diǎn)間相互作用進(jìn)行驗(yàn)證，并進(jìn)一步采用脂多糖（LPS）致ALI大鼠模型，借助實(shí)時(shí)熒光半定量聚合酶鏈?zhǔn)椒磻?yīng)（qRT-PCR）明確桑菊飲對ALI大鼠重要靶點(diǎn)（TNF、EGFR、STAT3、PTGS2）的調(diào)控作用。結(jié)果 共檢測出38個(gè)桑菊飲入血成分，獲得220個(gè)藥物潛在靶點(diǎn)、3 758個(gè)ALI治療潛在靶點(diǎn)和145個(gè)交集靶點(diǎn)，篩選出 10個(gè)核心成分（蘆丁、苦杏仁苷、甘草苷等）。KEGG通路富集分析揭示桑菊飲可能通過影響花生四烯酸代謝、PI3K-Akt信號通路等多種生命過程，發(fā)揮抗ALI作用。分子對接結(jié)果表明，蘆丁、苦杏仁苷、甘草苷等核心成分與TNF、EGFR、STAT3等關(guān)鍵靶點(diǎn)具有良好親和力。qRT-PCR結(jié)果進(jìn)一步顯示桑菊飲可顯著回調(diào)ALI導(dǎo)致的EGFR、TNF、STAT3、PTGS2 等 mRNA 表達(dá)量的改變（P＜0.01）。結(jié)論 桑菊飲可能通過甘草苷、蘆丁、苦杏仁苷等多成分干預(yù) TNF、EGFR、STAT3、PTGS2等多靶點(diǎn)，進(jìn)而調(diào)節(jié)花生四烯酸代謝和PI3K-Akt等信號通路發(fā)揮治療ALI作用。

Objective To explore the mechanism of Sangju Yin in the treatment of acute lung injury (ALI). Methods The ultra-high performance liquid chromatography coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESIQTOF-MS/MS) was used to quickly identify the components of Sangju Yin absorbed in plasma. Swiss Target Prediction and GeneCards were used to screen the related targets of Sangju Yin's plasmatic components and ALI-related targets, and the potential targets of Sangju Yin's anti-ALI were confirmed by Venny. Metascape was used to analyze the pathway of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) at the intersection target, and the protein-protein interaction network (PPI) was constructed and analyzed by String database and Cytoscape software. Based on molecular docking, the interactions between important components and targets were validated. The LPS-induced ALI rat model was conducted to clarify the regulatory effects of Sangju Yin on key targets (TNF, EGFR, STAT3, and PTGS2) in rats, using real-time fluorescent semi-quantitative polymerase chain reaction (qRT-PCR). Results A total of 38 plasmatic components of Sangju Yin were detected, and 220 drug potential targets, 3 758 ALI treatment potential targets and 145 intersection targets were obtained, and 10 core components (rutin, amygdalin, liquiritin, etc.) were screened out. KEGG pathway enrichment analysis revealed that Sangju Yin may play the anti-ALI role by affecting arachidonic acid metabolism, PI3K-Akt signaling pathway and other life processes. The results of molecular docking showed that the core components such as rutin, amygdalin and liquiritin had good affinities with key targets such as TNF, EGFR and STAT3. The results of qRT-PCR further showed that Sangju Yin could significantly reverse the changes of mRNA expression of EGFR, TNF, STAT3 and PTGS2 induced by ALI (P<0.01). Conclusion Sangju Yin may interfere with TNF, EGFR, STAT3, PTGS2 and other targets through glycyrrhizin, rutin, amygdalin and other components, then regulate arachidonic acid metabolism and PI3K-Akt signal pathways to play the crucial role in treating ALI.

R285.5

國家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（82405233）；黑龍江省自然科學(xué)基金聯(lián)合引導(dǎo)項(xiàng)目（LH2021H124）；黑龍江省大學(xué)生創(chuàng)新訓(xùn)練計(jì)劃項(xiàng)目（S202211230035，202111230032，S202211230055）；齊齊哈爾市科技計(jì)劃聯(lián)合引導(dǎo)項(xiàng)目（LHYD-2021011）；齊齊哈爾醫(yī)學(xué)科學(xué)院重點(diǎn)培育項(xiàng)目（2022-ZDPY-004，2023-ZDPY-001）；齊齊哈爾醫(yī)學(xué)科學(xué)院青年博士專項(xiàng)科研基金項(xiàng)目（QM‐SI2021B-03）；齊齊哈爾醫(yī)學(xué)科學(xué)院博士滾動(dòng)項(xiàng)目（QMSI2023E-01）