基于网络药理学的松花粉调节高脂血症机制探讨

Mechanism of Pini Pollen in Regulating Hyperlipidemia Based on Network Pharmacology

目的:基于网络药理学方法研究松花粉对高脂血症治疗的潜在作用机制。方法:检索中药系统药理学数据库与分析平台、中国知网、PubMed数据库,获取中药松花粉化学成分;利用PubChem数据库将成分标准化,并导入SwissTargetPrediction数据库筛选其潜在作用靶点;通过GeneCards、OMIM数据库获得高脂血症相关潜在靶点;利用Venny软件将所得松花粉相关靶点与高脂血症相关靶点取交集,并使用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络模型和成分-靶点网络;通过Metascape平台进行交集靶点的基因本体富集分析及京都基因和基因组百科全书富集分析。结果:松花粉治疗高脂血症关键活性成分为山柰酚、香橙素、β-谷甾醇、花旗松素等,关键靶点蛋白有类视黄醇X受体α(RXRA)、β-淀粉样蛋白前体蛋白(APP)、血管内皮生长因子(VEGFA)、蛋白激酶B1(Akt1)、磷脂酰肌醇3-激酶调节亚基α(PIK3R1)、甲状腺素运载蛋白(TTR)、过氧化物酶体增殖物激活受体α(PPARA)等。松花粉治疗高脂血症的通路主要涉及缺氧诱导因子-1(HIF-1)信号通路、PPAR信号通路、卵巢类固醇及类固醇生物生成、脂肪细胞脂解调节、胆汁分泌、胰高血糖素信号通路、脂肪消化和吸收等通路,其主要分子和生物功能主要与脂质结合、类固醇代谢、炎症反应、脂质应答、激素调节等相关。结论:研究结果初步说明了松花粉治疗高脂血症可能的作用机制,体现了松花粉多靶点、多通路、联合调控、调节平衡的作用特点,为松花粉相关药物开发和临床应用提供参考。

Objective:To explore the underlying mechanism of Pini Pollen in the treatment of hyperlipidemia based on network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,CNKI,and PubMed were searched for the chemical constituents of Pini Pollen.The chemical constituents were standardized by PubChem and then imported into SwissTargetPrediction to screen the potential targets.Potential targets related to hyperlipidemia were obtained through GeneCards and OMIM.The common targets of Pini Pollen and hyperlipidemia were screened out by Venny,and STRING and Cytoscape were used to construct the protein-protein interaction(PPI)network model and component-target network.Finally,the Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the common targets were carried out on the Metascape platform.Results:The key active components of Pini Pollen in the treatment of hyperlipidemia were kaempferol,aromadendrin,β-phytosterol,and taxifolin.The key target proteins included retinoid X receptor alpha(RXRA),amyloid-beta precursor protein(APP),vascular endothelial growth factor A(VEGFA),RAC-alpha serine/threonine-protein kinase(Akt1),phosphatidylinositol 3-kinase regulatory subuni1(PIK3R1),transthyretin(TTR),and peroxisome proliferator-activated receptor alpha(PPARA).The pathways of Pini Pollen in the treatment of hyperlipidemia mainly involved hypoxia-inducible factor-1(HIF-1)signaling pathway,PPAR signaling pathway,ovarian steroids and steroid biogenesis,adipocyte lipolysis regulation,bile secretion,glucagon signaling pathway,fat digestion,absorption,and other pathways.Its main molecular and biological functions were mainly related to lipid binding,steroid metabolism,inflammatory response,lipid response,hormone regulation,etc..Conclusion:The results preliminarily demonstrated the underlying mechanism of Pini Pollen in the treatment of hyperlipidemia and reflected the characteristics of multi-target,multi-pathway,combined regulation and balance of Pini Pollen,providing a theoretical basis for drug development and clinical application of Pini Pollen.