目的 基于超高效液相色谱-线性离子阱串联静电场轨道高分辨质谱（UHPLC-LTQ-Orbitrap-MS/MS）技术、网络药理学和分子对接探究蒲公英改善高脂血症的有效成分及其作用机制。方法 根据质谱信息结合对照品裂解规律并参考文献指认蒲公英中化学成分；利用STITCH、SwissTargetPredection、TCMSP数据库构建蒲公英的潜在药效成分靶点数据库，通过GeneCards、DrugBank、OMIM、TherapeuticTargetDatabase、PharmGKB获取血脂异常潜在靶点；使用STRING数据库构建关键靶点蛋白相互作用（PPI）网络；通过Metascape数据库对关键靶点进行基因本体论（GO）功能与京都基因与基因组百科全书（KEGG）信号通路富集分析；借助Cytoscape软件构建"活性成分-靶点-通路"网络；采用分子对接技术进行虚拟验证。结果 从蒲公英中共鉴别出126个化合物，包括黄酮类58个，有机酸类29个，萜类23个，苯丙素8个，核苷类3个和其他类5个。网络药理学研究表明，蒲公英可能通过槲皮素、异鼠李素、香叶木素、白杨素、芹菜素等成分作用于碳酸酐酶2（CA2）、碳酸酐酶7（CA7）、醛糖还原酶（AKR1B1）、基质金属蛋白酶2（MMP-2）、蛋白激酶1（Akt1）等核心靶点，来调节脂质和动脉粥样硬化、磷脂酰肌醇-3-激酶（PI3K）/Akt、丝裂原活化蛋白激酶（MAPK）、流体剪切应力和动脉粥样硬化和晚期糖基化终末产物（AGE）/AGEs受体（RAGE）等信号通路，从而发挥调血脂作用；分子对接验证结果表明，蒲公英改善高脂血症有效成分与疾病靶点蛋白具有较强的结合活性。结论 蒲公英可能通过调控脂质代谢、炎症反应、内质网应激、氧化应激和免疫调节等多方面发挥改善高脂血症的作用。

Objective To investigate the active components and its mechanism for improving hyperlipidemia of Taraxacum mongolicum Hand.-Mazz. using UHPLC-LTQ-Orbitrap-MS/MS, network pharmacology and molecular docking. Methods Chemical composition of Taraxacum mongolicum was identified by mass spectrometry information combined with the fragmentation patterns of reference compounds and references. Potential pharmacological targets of Taraxacum mongolicum were screened using STITCH, SwissTargetPrediction, and TCMSP databases, while potential targets for dyslipidemia were obtained from GeneCards, DrugBank, OMIM, TherapeuticTarget, and PharmGKB Database. PPI network of key targets was constructed using STRING database. Key targets were subjected to GO and KEGG pathway enrichment analysis using Metascape database. The active ingredient-target-pathway network was built using Cytoscape software. Finally, molecular docking verification was performed between the active ingredients and the key targets. Results A total of 126 compounds were identified from Taraxacum mongolicum, including 58 flavonoids, 29 organic acids, 23 terpenes, 8 coumarins, 3 nucleosides, and 5 other compounds. Network pharmacology studies showed that Taraxacum mongolicum may act on CA2, CA7, AKR1B1, MMP-2, AKT1, and other core targets through quercetin, isorhamnetin, diosmetin, chrysin, apigenin, and other components. It regulates lipid and atherosclerosis, PI3K/Akt, MAPK, fluid shear stress and atherosclerosis, and AGE/RAGE signaling pathways to play a role in regulating blood lipids. Molecular docking validation results demonstrate that the active components exhibit strong binding activity with disease target proteins. Conclusion Taraxacum mongolicum may play a role in improving hyperlipidemia by regulating lipid metabolism, inflammatory response, endoplasmic reticulum stress, oxidative stress and immunomodulation.

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国家自然科学基金青年基金资助项目（81503244）；北京中医药大学纵向发展基金项目（2019-ZXFZJJ-052）