目的 利用網(wǎng)絡(luò)藥理學(xué)、分子對接技術(shù)研究松三糖治療肝纖維化潛在機制，并對核心靶點進行實驗驗證。方法 從Swiss Target Prediction數(shù)據(jù)庫中篩選松三糖治療疾病相關(guān)靶點；從OMIM、GeneCards、Disgenet數(shù)據(jù)庫中篩選出肝纖維化的相關(guān)靶點。對STRING數(shù)據(jù)庫進行蛋白質(zhì)相互作用網(wǎng)絡(luò)，將tsv格式數(shù)據(jù)結(jié)果導(dǎo)入Cytoscape 3.9.1軟件中進行可視化分析。進一步使用DAVID數(shù)據(jù)庫對交集靶點進行基因本體（GO）分析和京都基因和基因組的百科全書（KEGG）富集分析，并進行分子對接。通過MTT法檢測小鼠肝星狀細(xì)胞系JS-1細(xì)胞活力；Western blotting驗證核心靶點的蛋白表達水平。結(jié)果 KEGG富集分析顯示交集靶點涉及信號通路64條，主要為磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）、絲裂原活化蛋白激酶（MAPK）信號通路。分子對接提示松三糖與核心靶點能較好結(jié)合。Western blotting結(jié)果顯示，在不同濃度松三糖作用下，JS-1細(xì)胞中磷酸化的PI3K/Akt以及MAPK的蛋白表達量均顯著降低。結(jié)論 松三糖可能通過作用于PI3K/Akt及MAPK等多個靶點，發(fā)揮抗肝纖維化作用。

Objective To investigate the mechanisms of the melezitose in treating liver fibrosis using network pharmacology and molecular docking techniques, and to validate the core targets. Methods The related targets of melezitose in treatment of liver fibrosis were screened from the Swiss Target Prediction database. The related targets of liver fibrosis were screened from OMIM, GeneCards and Disgenet databases. The protein interaction network was carried out on the STRING database, and the tsv format data results were imported into Cytoscape 3.9.1 software for visual analysis. DAVID database was further used for GO analysis and KEGG enrichment analysis, and molecular docking. The viability of mouse hepatic stellate cell line JS-1 was measured by MTT assay. Western blotting verified the protein expression level of the core target. Results KEGG enrichment analysis showed that the intersection targets involved 64 signaling pathways, mainly PI3K/Akt and MAPK signaling pathways. Molecular docking suggested that pine triose could bind well to the core target. Western blotting results showed that the phosphorylated PI3K/Akt and MAPK protein expressions in cells were significantly reduced under the influence of different concentrations of melezitose. Conclusion Melezitose may exert anti-liver fibrosis effects by acting on multiple targets such as PI3K/Akt and MAPK.

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新疆維吾爾自治區(qū)重大科技專項項目(2022A03019-3);新疆維吾爾自治區(qū)自然科學(xué)基金資助項目(2022D01D37)