| 引用本文:罗绍东，张文风，王杨，研智，李岩珂.基于网络药理学预测橘皮竹茹汤防治化疗性呕吐的作用机制及验证研究[J].世界中医药,2024,(19):. |
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| 基于网络药理学预测橘皮竹茹汤防治化疗性呕吐的作用机制及验证研究 |
| Mechanism and Validation of Jupi Zhuru Decoction in the Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting Based on Network Pharmacology |
| 投稿时间：2023-10-13 |
| DOI：10.3969/j.issn.1673-7202.2024.19.001 |
| 中文关键词: 橘皮竹茹汤 网络药理学 分子对接 化疗性呕吐 糖原合酶激酶3β 蛋白激酶B 5-羟色胺 单胺氧化酶A 色氨酸羟化酶 |
| English Keywords:Jupi Zhuru Decoction Network pharmacology Molecular docking CINV GSK-3β AKT 5-HT MAOA TPH |
| 基金项目:国家社科基金应急管理体系建设研究专项项目（20VYJ070）；吉林省医药健康产业发展专项切块资金项目（20230404002TH） |
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| 中文摘要: |
| 目的：基于网络药理学预测橘皮竹茹汤防治化疗性呕吐（CINV）的活性成分、作用靶点及信号通路，并通过分子对接、动物实验探讨其止呕的作用机制。方法：通过中药系统药理学数据库与分析平台（TCMSP）、Ctd数据库选取橘皮竹茹汤活性成分，与Uniprot、DisGeNET、GeneCard数据库获取的CINV相关靶点进行拟合筛选。利用Cytoscape软件构建复方活性成分-靶点-疾病网络，String数据库构建蛋白质-蛋白质相互作用（PPI）网络，并进行网络拓扑学分析。通过Metascape、微生信数据库可视化基因本体（GO）、京都基因和基因组百科全书（KEGG）富集分析数据，并获取关键蛋白，利用AutoDock、PYMOL软件进行分子对接验证。最后通过造模和药物对大鼠进行干预后，记录大鼠高岭土摄食量，检测延髓、回肠病理学改变；测定延髓、回肠蛋白激酶B（AKT）、糖原合酶激酶3β（GSK-3β）蛋白含量及呕吐神经递质5-羟色胺（5-HT）、色氨酸羟化酶（TPH）、单胺氧化酶A（MAOA）的表达水平。结果：获取橘皮竹茹汤活性成分141个，79个复方-疾病交集基因，9个核心靶点，其止呕作用可能与诱导AKT胞膜移位，抑制GSK-3在Ser9/21位点磷酸化有关。动物实验显示橘皮竹茹汤可降低化疗性呕吐大鼠的高岭土异嗜量、减轻肠道炎症；上调延髓、回肠AKT水平，抑制GSK-3、表达；抑制延髓、回肠TPH合成酶，促进MAOA代谢酶，从而减少5-HT表达量。结论：橘皮竹茹汤可通过调控AKT/GSK-3β信号通路，抑制回肠、延髓中GSK-3β含量表达，对CINV起防治作用；还可抑制延髓、回肠TPH合成酶，促进MAOA代谢酶分泌，达到止呕功效。 |
| English Summary: |
| To predict the active ingredients，target genes，and signaling pathways of Jupi Zhuru Decoction in preventing and treating chemotherapy-induced nausea and vomiting(CINV) based on network pharmacology，and to explore its anti-emetic mechanism through molecular docking and animal experiments.Methods:The active ingredients of Jupi Zhuru Decoction were selected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Ctd database.CINV-related target genes were obtained from the Uniprot，DisGeNET，and GeneCard databases.Network fitting and screening were performed between the active ingredients and CINV-related targets.The active ingredient-target-disease network was constructed using Cytoscape software，and protein-protein interaction(PPI) network was built using the String database and topological analysis was conducted.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were visualized using Metascape and MicroBing databases，followed by identification of key proteins.Molecular docking validation was performed using AutoDock and PYMOL software.In animal experiments，rats were modeled for CINV and treated with the drug.The kaolin intake of rats was measured，and histopathological changes in the medulla oblongata and ileum were observed.The expression levels of protein kinase B(AKT)，glycogen synthase kinase-3β(GSK-3β)，serotonin(5-HT)，tryptophan hydroxylase(TPH)，and monoamine oxidase A(MAOA) were assessed.Results:A total of 141 active ingredients from Jupi Zhuru Decoction were identified，and 79 intersection genes between the compound and disease were obtained，with 9 core targets.The anti-emetic effects may be related to the induction of AKT membrane translocation and inhibition of GSK-3 phosphorylation at Ser9/21.Animal experiments showed that Jupi Zhuru Decoction reduced kaolin intake and alleviated intestinal inflammation in CINV rats.It also upregulated AKT levels in the medulla oblongata and ileum，inhibited GSK-3 expression，suppressed TPH synthesis in the medulla oblongata and ileum，and promoted the secretion of MAOA，resulting in reduced 5-HT expression.Conclusion:Jupi Zhuru Decoction can prevent and treat CINV by regulating the AKT/GSK-3β signaling pathway to inhibit GSK-3β expression in the medulla oblongata and ileum.It also inhibits TPH synthesis and promotes MAOA secretion，achieving anti-emetic effects. |
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