机构地区:[1]广州中医药大学第二临床医学院,广东广州510405 [2]广东省中医院,广东广州510120
出 处:《海南医学院学报》2020年第13期1019-1027,共9页Journal of Hainan Medical University
基 金:中医药行业科研专项项目(201507001-02);国家中医药管理局课题(1199ws02):李丽芸全国名老中医药专家传承工作室.
摘 要:目的:基于网络药理学方法,探讨寿胎丸干预治疗先兆流产的作用机制。方法:通过TCMSP数据库、BATMAN-TCM数据库及Uniprot数据库获得寿胎丸中有效的活性成分及作用靶点,在GeneCards中检索“threatened abortion”得到先兆流产相关的疾病靶点,通过韦恩图进行基因映射得到寿胎丸与先兆流产共同作用的靶点基因,并用Cytoscape软件构建“疾病-药物-靶点”互相作用网络。将疾病与药物共同作用的靶标上传至STRING数据库,构成蛋白互作网络图(PPI),使用R语言对得到的PPI进行关键基因的筛选。最后运用R语言进行GO富集分析和KEGG通路富集分析。结果:预测得到寿胎丸治疗先兆流产的有效活性成分21个及共同有效靶点89个,有效成分中度值较高的是檞皮素(quercetin)、山奈酚(kaempferol)、β-谷甾醇(beta-sitosterol)和异鼠李素(isorhamnetin);靶点中度值较高的是前列腺素内过氧化物酶受体(PTGS2)、孕激素受体(PGR)、前列腺素内过氧化物酶受体1(PTGS1)、过氧化物酶体增生剂激活受体γ(PPARG)。PPI网络中核心靶点为白细胞介素6(IL-6)、蛋白激酶(AKT1)、血管内皮生长因子A(VEGFA)等;GO富集分析显示会影响细胞因子的活性、调节功能,核蛋白受体以及基因的转录等;KEGG通路富集分析显示糖尿病并发症中的糖化终末产物及其受体信号通路显著性最高,其次是流体剪切应力和动脉粥样硬化通路。结论:寿胎丸主要通过调节细胞因子,从而达到抗炎、增强血管通透性、改善子宫内膜容受性等多方面调控有助于早期胚胎着床。Objective:To explore the mechanism of ShouTaiWan's intervention in the treatment of threatened abortion based on network pharmacology.Methods:The effective active ingredients and targets in ShouTaiWan were obtained by searching in databases including TCMSP,BATMAN-TCM and Uniprot.The target of threatened abortion was obtained by searching for'threatened abortion'in GeneCards.And the co-target gene of ShouTaiWan and threaten abortion can be obtained through the use of gene mapping in Venn diagram.Then an interaction network"disease-drug-target"can be constructed by Cytoscape.This study uploaded the Co-targeted gene to the STRING database to construct the protein interaction network map(PPI),which would be screened for the key genes by using R language.Finally,this study used the R language to analyze gene ontology(GO)enrichment and kyoto encyclopedia of genes and genome(KEGG)pathway enrichment.Result It is predicted that 21 effective active ingredients for the treatment of threatened abortion and 89 common effective targets are expected.Quercetin,kaempferol,beta-sitosterol,and isorhamnetin were the most effective components.As for the targets,prostaglandin endoperoxidase receptor(PTGS2),progesterone receptor(PGR),prostaglandin endoperoxidase receptor 1(PTGS1),and peroxisome proliferator activates receptor gamma(PPARG)were the most effective ones.The core targets in PPI network are Interleukin-6(IL-6),protein kinase(AKT1),vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis shows that the activity of cytokines,regulatory functions,nuclear protein receptors and transcription of genes would be affected.KEGG pathway enrichment analysis illustrates that advanced glycation end products-receptor for AGE(AGE-RAGE)pathways are of the highest significance,followed by the fluid shear stress and atherosclerosis pathways.Conclusion:ShouTaiWan can achieve anti-inflammatory,increase vascular permeability,improve endometrial receptivity and other aspects of regulation to treat threatened abortion and embryo impla
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