【摘要】 目的 基于网络药理学探讨调脂消斑方治疗高脂血症合并动脉粥样硬化的作用机制。方法 使用TCMSP数据库确定调脂消斑方的活性成分和作用靶点;采用GeneCard、OMIM数据库筛选高脂血症和动脉粥样硬化的疾病靶点,应用Venny 2.1平台获取药物与疾病的交集靶点,预测调脂消斑方治疗高脂血症合并动脉粥样硬化的潜在作用靶点;应用String数据库构建交集靶点的蛋白质-蛋白质相互作用(PPI)网络,筛选获得核心作用靶点;将交集靶点进行基因本体论(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析;利用Cytoscape 3.7.2软件绘制“核心活性成分-核心靶点-核心通路-疾病”网络。并对核心活性成分与核心靶点进行分子对接验证。结果 共筛选出调脂消斑方潜在活性成分272个,可用于高脂血症合并动脉粥样硬化治疗的靶点127个;并筛选得丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤坏死因子(TNF)、白细胞介素-6 (IL-6)、白细胞介素-1β(IL-1β)、TP53等13个核心靶点与槲皮素、β-谷甾醇、山奈酚等29个核心活性成分;GO分析富集得到生物学过程(BP)相关条目2 040条、细胞组分(CC)相关条目79条、分子功能(MF)相关条目202条。KEGG通路富集分析共得到189条相关信号通路,主要涉及AGE-RAGE信号通路、脂质和动脉粥样硬化、白细胞介素-17(IL-17)信号通路等。分子对接结果显示,槲皮素与核心靶点AKT1、TNF、IL-6、IL-1β、TP53的对接亲和力均<-5.0 kcal/mol,提示药物成分与核心靶点间具有较好的结合活性。结论 调脂消斑方防治高脂血症和动脉粥样硬化具有多成分、多靶点、多通路的作用特点。通过网络药理学分析可为其降脂、抗动脉粥样硬化的药理作用机制提供理论依据。更多还原

【Abstract】 Objective To explore the mechanism of action of the lipid-regulating and spot-reducing formula in the treatment of hyperlipidemia combined with atherosclerosis based on network pharmacology.Methods The TCMSP database was used to identify the active ingredients and targets of the lipid-regulating and spot-reducing formula.Disease targets for hyperlipidemia and atherosclerosis were selected from the GeneCard and OMIM databases.The Venny 2.1 platform was used to obtain the intersection targets of the drug and the disease,and potential therapeutic targets for hyperlipidemia combined with atherosclerosis were predicted.The String database was used to construct a protein-protein interaction(PPI) network for the intersection targets and identify the core targets.Gene ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the intersection targets.Cytoscape 3.7.2 software was used to construct a " core active ingredient-core target-core pathway-disease" network.Molecular docking was performed to validate the interaction between core active ingredients and core targets.Results A total of 272 potential active ingredients were identified for the lipid-regulating and spot-reducing formula,which could act on 127 targets related to hyperlipidemia combined with atherosclerosis.Overall,13 core targets,including AKT Serine/Threonine Kinase 1(AKT1),tumor necrosis factor(TNF),interleukin-6(IL-6),interleukin-1 beta(IL-1β),and TP53,were selected,which interacted with 29 core active ingredients,including quercetin,β-sitosterol,and kaempferol.GO analysis showed 2,040 biological process(BP) entries,79 cellular component(CC) entries,and 202 molecular function(MF) entries.KEGG pathway enrichment analysis revealed 189 related signaling pathways,mainly involving the AGE-RAGE signaling pathway,lipid metabolism and atherosclerosis,and IL-17 signaling pathways.Molecular docking results showed that the binding affinity between quercetin and the core targets AKT1,TNF,IL-6,IL-1β,and TP53 was <-5.0 kcal/mol,suggesting good binding activity between the drug components and core targets.Conclusion The lipid-regulating and spot-reducing formula has a multi-component,multi-target,and multi-pathway action profile in the prevention and treatment of hyperlipidemia and atherosclerosis.Network pharmacology analysis provides theoretical support for its lipid-lowering and anti-atherosclerosis pharmacological mechanisms.更多还原