目的 研究桑菊飲治療急性肺損傷（ALI）的作用機制。方法 采用超高效液相色譜-電噴霧串聯(lián)四極桿飛行時間質譜法（UHPLC-ESI-QTOF-MS/MS）快速鑒別桑菊飲的入血成分，使用 Swiss Target Prediction和 GeneCards等數據庫篩選桑菊飲入血成分關聯(lián)靶點與ALI相關靶點，并通過Venny確認桑菊飲抗ALI潛在靶點。使用Metascape對交集靶點進行基因本體（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數據庫與Cytoscape軟件構建并分析蛋白質-蛋白質相互作用（PPI）網絡。基于分子對接對重要成分和靶點間相互作用進行驗證，并進一步采用脂多糖（LPS）致ALI大鼠模型，借助實時熒光半定量聚合酶鏈式反應（qRT-PCR）明確桑菊飲對ALI大鼠重要靶點（TNF、EGFR、STAT3、PTGS2）的調控作用。結果 共檢測出38個桑菊飲入血成分，獲得220個藥物潛在靶點、3 758個ALI治療潛在靶點和145個交集靶點，篩選出 10個核心成分（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。分子對接結果表明，蘆丁、苦杏仁苷、甘草苷等核心成分與TNF、EGFR、STAT3等關鍵靶點具有良好親和力。qRT-PCR結果進一步顯示桑菊飲可顯著回調ALI導致的EGFR、TNF、STAT3、PTGS2 等 mRNA 表達量的改變（P＜0.01）。結論 桑菊飲可能通過甘草苷、蘆丁、苦杏仁苷等多成分干預 TNF、EGFR、STAT3、PTGS2等多靶點，進而調節(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.

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國家自然科學基金青年科學基金項目（82405233）；黑龍江省自然科學基金聯(lián)合引導項目（LH2021H124）；黑龍江省大學生創(chuàng)新訓練計劃項目（S202211230035，202111230032，S202211230055）；齊齊哈爾市科技計劃聯(lián)合引導項目（LHYD-2021011）；齊齊哈爾醫(yī)學科學院重點培育項目（2022-ZDPY-004，2023-ZDPY-001）；齊齊哈爾醫(yī)學科學院青年博士專項科研基金項目（QM‐SI2021B-03）；齊齊哈爾醫(yī)學科學院博士滾動項目（QMSI2023E-01）