| 方珍珍,胡雨桐,郑妍,等.祛浊通痹方治疗肥胖有效成分和潜在机制探究[J].浙江中医药大学学报,2023,47(10):1115-1122. |
| 祛浊通痹方治疗肥胖有效成分和潜在机制探究 |
| Active Components and Potential Mechanism of Quzhuo Tongbi Formula in Treatment of Obesity Based on Network Pharmacology |
| DOI：10.16466/j.issn1005-5509.2023.10.001 |
| 中文关键词: 网络药理学 祛浊通痹方 肥胖 基因靶点 作用机制 实验验证 |
| 英文关键词: network pharmacology Quzhuo Tongbi Formula obesity gene targets mechanism experimental verification |
| 基金项目:国家自然科学基金联合基金重点支持项目(U21A20402)；浙江省中医药传承创新项目(2023ZF205) |
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| 中文摘要: |
| [目的] 基于网络药理预测祛浊通痹方(Quzhuo Tongbi，QZTB)治疗肥胖的有效成分和潜在机制，并采用肥胖模型小鼠验证其效果。[方法] 利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)筛选QZTB有效成分及靶点，检索DrugBank、人类基因组注释数据库(Human Genome Annotation Database，GeneCards)和在线人类孟德尔遗传(Online Mendelian Inheritance in Man，OMIM)数据库收集肥胖的相关靶点，利用Venny 2.1在线平台筛选QZTB治疗肥胖的交集靶点，并制作韦恩图，根据STRING 11.5数据库构建蛋白互作(protein-protein interaction，PPI)网络图，借助网络拓扑分析(Cytoscape network centrality analysis，CytoNCA)插件筛选QZTB治疗肥胖的核心靶点。利用Cytoscape 3.8.2软件建立“中药-成分-靶点-疾病” 模型，筛选QZTB治疗肥胖的有效成分，并基于Metascape在线数据库对交集靶点进行基因本体(gene ontology，GO)功能和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomics，KEGG)通路富集分析，通过Python对结果进行可视化。将C57BL/6雄性小鼠随机分为空白组、模型组和QZTB组，通过高脂饲料诱导肥胖模型，灌胃给药10周后分离肝脏组织进行病理学检查，采用实时荧光定量聚合酶链式反应(Real-time quantitative polymerase chain reaction，Real-time qPCR)法检测肝组织丝氨酸/苏氨酸蛋白激酶1(serine/threonine protein kinase 1，AKT1)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)和白细胞介素-6(interleukin-6，IL-6)的mRNA表达水平。[结果] 通过靶点交集和PPI网络，筛选出QZTB治疗肥胖的重要靶点31个，其中AKT1、TNF-α和IL-6为核心靶点。槲皮素、落新妇苷、柚皮素和小檗碱可能是QZTB防治肥胖的关键成分。GO功能富集分析主要作用于细胞迁移的正调控、细胞对化学应激的反应生物过程、膜筏细胞成分和转录因子结合等分子功能途径，KEGG通路富集分析提示主要涉及晚期糖基化终产物及受体(advanced glycation end products-receptor for advanced glycation end products，AGE-RAGE)信号通路、脂质与动脉粥样硬化和胰岛素抵抗等通路。与模型组比较，QZTB可以明显改善雄性肥胖小鼠肝组织病变，明显升高AKT1的mRNA表达水平(P<0.01)，显著降低TNF-α和IL-6的mRNA表达水平(P<0.01，P<0.001)。[结论] QZTB可通过槲皮素、落新妇苷、柚皮素和小檗碱等活性成分，调控AKT1、TNF-α和IL-6等靶点表达，从而达到治疗肥胖的效果，为进一步探究临床治疗肥胖型痛风提供了科学依据。 |
| 英文摘要: |
| [Objective] To explore the active components and potential mechanism of Quzhuo Tongbi Formula(QZTB) in treatment of obesity based on network pharmacology and validate the effects. [Methods] The targets were screened related to QZTB from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and collected from DrugBank， Human Genome Annotation Database(GeneCards) and Online Mendelian Inheritance in Man(OMIM) database. The intersected targets of QZTB for treating obesity were screened for a VENN diagram by using Venny 2.1 online platform to construct a protein-protein interaction(PPI) network based on the STRING 11.5 database. The Chinese herb-component-target-disease network was constructed by using Cytoscape 3.8.2 software and Cytoscape network centrality analysis(CytoNCA). Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics(KEGG) enrichment analysis were performed by Metascape database. C57BL/6 male mice were randomly divided into blank group， model group and QZTB group， high-fat diet was fed for moulding and administered by gavage for 10 weeks. The mRNA expression levels of serine/threonine protein kinase 1(AKT1)， tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in liver tissues were measured by Real-time quantitative polymerase chain reaction(Real-time qPCR). [Results] Through target intersection and PPI network，31 important targets of QZTB for treating obesity were obtained， among which AKT1， TNF-α and IL-6 are the core targets. Quercetin， astirin， naringin and berberine may be the key components for QZTB in preventing obesity. GO enrichment analysis involved in positive regulation of cell migration， membrane raft and transcription factor binding. KEGG pathway analysis indicated that it mainly involved the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE) signaling pathway， lipid and atherosclerosis and insulin resistance， etc. Compared with model group， QZTB treatment improved the change in fat liver tissue， upregulated the mRNA levels of hepatic AKT1(P<0.01) and downregulated the mRNA levels of TNF-α and IL-6 in liver tissue(P<0.01，P<0.001). [Conclusion] QZTB could treat obesity through regulating the expression levels of the targets of AKT1， TNF-α and IL-6 by active ingredients such as quercetin， astiltin， naringin and berberine， etc. It provides a scientific basis to further explore the clinical treatment of obese gout. |
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