基于网络药理学预测柳蒿芽脂溶性部位的降血脂作用及实验验证*

作者：明 慧，王青虎，何 祥，伊力奇

单位：内蒙古民族大学蒙医药学院，内蒙古 通辽 028000

引用：引用：明慧，王青虎，何祥，伊力奇.基于网络药理学预测柳蒿芽脂溶性部位的降血脂作用及实验验证[J].中医药导报,2025,31(4):53-59.

DOI：10.13862/j.cn43-1446/r.2025.04.009

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摘要：目的：探讨柳蒿芽脂溶性部位（LPAI）对高脂血症（HLP）的降血脂作用。方法：通过Swiss Target Prediction和SEA数据库对LPAI中收集的20个化学成分进行靶点预测，在TTD和GeneCards中获取HLP靶点。利用微生信对基因进行匹配并绘制韦恩图，获得LPAI治疗HLP的潜在靶标。通过String网站绘制靶蛋白PPI网络图，通过Metascape数据库进行基因本体论（GO）富集分析和京都基因与基因百科组全书（KEGG)通路富集分析。利用Cytoscape 3.6.0软件构建药物-靶点-作用通路网络。采用LPAI干预以FFA诱导L-02细胞脂肪变性模型对核心靶点和通路进行验证，观察LPAI对L-02细胞增殖、细胞内脂滴及甘油三酯（TG）含量的影响，并用Western blotting检测关键通路中过氧化物酶体增殖物激活受体α（PPARα）和脂蛋白脂酶（LPL）蛋白的表达水平。结果：筛选得到LPAI与HLP关联的潜在靶点84个。GO功能富集分析获得662个条目，其中生物过程614条，分子功能31条，细胞组分17条。KEGG通路富集分析显示，LPAI治疗HLP的主要信号通路包括PPAR信号通路、胰岛素抵抗、脂肪细胞因子信号通路等。CCK-8实验显示，LPAI可抑制FFA诱导的L-02细胞增殖，并与剂量和时间有依赖性。油红O染色实验显示，LPAI低、中、高剂量组细胞内脂滴分布在细胞膜边缘，累积数量逐渐减少，且细胞内脂滴伴有不同程度的改善现象。模型组TG含量高于对照组（P<0.01）；LPAI中、高剂量组TG含量低于模型组（P<0.05或P<0.01）。模型组PPARα和LPL蛋白相对表达量低于对照组（P<0.01或P<0.05）；LPAI低、中、高剂量组LPL蛋白相对表达量高于模型组（P<0.05）；LPAI中剂量组PPARα蛋白相对表达量高于模型组（P<0.05）。结论：LPAI具有降血脂作用，可通过调控PPAR信号通路，抑制FFA诱导的L-02细胞中PPARα和LPL蛋白表达。

关键词：高脂血症；柳蒿芽；脂溶性部位；网络药理学；降血脂

Abstract：

Objective: To investigate the hypolipidemic effect of liposoluble parts from Artemisia integrifolia (LPAI). Methods: The target prediction of 20 chemical components collected from LPAI was carried out by Swiss Target Prediction and SEA database, and the hyperlipidemia (HLP) targets were obtained in TTD and GeneCards. The potential targets of LPAI for the treatment of HLP were obtained by using bioinformatics to match genes and draw Venn diagrams. The PPI network diagram was constructed on String website, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out through Metascape database. The Cytoscape 3.6.0 Software was used to build the network of compounds-targets-pathways for LPAI against HLP. Then, the core targets and pathways were preliminarily verified by the in vitro experiment of L-02 cell steatosis model induced by FFA after the intervention of LPAI. The effects of LPAI on proliferation of L-02 cells, the content of cell lactone drops and triglyceride (TG) were investigated, and Western blotting was used to detect expression of peroxisome proliferator activated receptor α (PPARα) and lipoprotein lipase (LPL). Results: Totally 84 potential targets that LPAI associated with HLP were screened. The functional enrichment analysis of GO obtained 662 GO items, including 614 biological processes, 31 molecular functions and 17 cellular components. KEGG pathway enrichment analysis showed that the main signal pathways of LPAI in the treatment of HLP include PPAR signal pathway, insulin resistance, adipocytokine signal pathway and so on. CCK-8 experiment showed that LPAI could reduce the proliferation of L-02 cells induced by FFA, which was dependent on dose and time. Oil red O staining experiment showed that the intracellular lipid droplets were distributed at the edge of cell membrane in LPAI low, medium and high dose groups, and that the cumulative number gradually decreased, accompanied by the improvement of different progress. The model groups showed higher TG content than control group (P<0.01). The LPAI medium and high dose groups showed lower TG content than model group (P<0.05 and P<0.01). The model group showed lower expression levels of PPAR α and LPL than control group (P<0.01 and P<0.05); The LPAI low, medium and high dose groups showed higher expression levels of LPL protein than model group (P<0.05), the LPAI medium dose group showed higher expression of PPAR α protein than model group (P<0.05). Conclusion: LPAI can reduce blood lipid and inhibit the expression of PPAR α and LPL in FFA-induced L-02 cells by regulating PPAR signal pathway.

Key words：hyperlipidemia; Artemisia integrifolia; liposoluble parts; network pharmacology; hypolipidemic effect

发布时间：2025-12-20

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