| 引用本文: | 董云怡,刘艺柯,邓晓琳,梁健.基于网络药理学和转录组学及实验验证探究菲牛蛭冻干粉抗高尿酸血症的作用机制[J].中国现代应用药学,2024,41(12):56-65. |
| Dong Yun Yi,Liu Yike,Deng Xiaolin,Liang Jian.Mechanism of SZ lyophilized powder on hyperuricemia based on network pharmacology, RNA-seq technology and experimental validationDong Yunyi 1, Liu Yike 1, Deng Xiaolin 1,Liang Jian 1*, (1. Guangxi University, Medical College, Nanning, 530004, China)[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(12):56-65. |
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| 摘要: |
| 目的：基于网络药理学和转录组学的方法，结合动物实验验证，探究菲牛蛭冻干粉（SZ）抗高尿酸血症（HUA）的多靶点作用机制。方法： 利用Symmap、 SwissTargetPrediction、Pharmmapper数据库，获得SZ潜在活性成分以及对应的靶点；通过Gene Cards和OMIM数据库获得HUA相关靶点；取交集映射得到SZ和HUA的共同靶点，利用Cytoscape 3.9.0软件构建药物成分-疾病靶点相互作用网络，结合STRING数据库构建蛋白相互作用网络并筛选核心靶点；使用DAVID数据库对交集靶点进行GO生物功能注释和KEGG通路富集分析。采用氧嗪酸钾联合高嘌呤饮食构建HUA小鼠模型，通过生化指标检测、ELISA法探究SZ对HUA小鼠的影响，qRT-PCR法验证RNA-Seq及网络药理学富集分析结果。结果：网络药理学分析表明SZ中有11种主要生物活性物质，72种潜在靶点参与治疗高尿酸血症，涉及多种生物过程和不同的信号通路。实验表明，SZ通过抑制XOD活性，显著降低了高尿酸血症小鼠的血清尿酸、肌酐和尿素氮水平。SZ还降低了尿酸盐转运蛋白1（URAT1）的水平，同时提高了ATP结合盒转运蛋白亚家族G成员2（ABCG2）的水平。RNA测序分析发现，模型组与治疗组、对照组与模型组和对照组与治疗组分别有112、536和107个差异表达基因（DEGs）。qRT-PCR结果表明，SZ下调了Th17细胞分化相关的基因以及IL-17和PI3K/Akt 信号通路上基因mRNA的表达。 结论：SZ具有降尿酸作用。其作用机制可能是抑制肝脏XOD活性，下调URAT1水平，上调ABCG2水平，影响Th17细胞的分化，进而影响IL-17信号通路，从而减轻炎症反应。 |
| 关键词: 高尿酸血症 水蛭 网络药理学 RNA-seq，传统中药 |
| DOI：10.13748/j.cnki.issn1007-7693.20230100 |
| 分类号: |
| 基金项目:基于METTL3介导m6A修饰调控EMT过程研究胃宁颗粒抑制胃癌细胞增殖 与侵袭转移的作用机制 |
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| Mechanism of SZ lyophilized powder on hyperuricemia based on network pharmacology, RNA-seq technology and experimental validationDong Yunyi 1, Liu Yike 1, Deng Xiaolin 1,Liang Jian 1*, (1. Guangxi University, Medical College, Nanning, 530004, China) |
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Dong Yun Yi, Liu Yike, Deng Xiaolin, Liang Jian
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广西大学
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| Abstract: |
| OBJECTIVE To investigate the multi-target mechanism of action of Shui Zhi lyophilized powder (SZ) against hyperuricemia (HUA) based on network pharmacology and transcriptomics approaches, combined with animal experiments. METHODS We identified the potential active ingredients and associated targets for SZ using the Symmap, SwissTargetPrediction, and Pharmmapper databases; obtained HUA-related targets by Gene Cards and OMIM databases. We then used intersection mapping to identify the shared targets between SZ and HUA. We used Cytoscape 3.9.0 software to construct the drug components-disease targets interaction network and combined it with the STRING database to generate the protein interaction network and screen core targets. The intersected targets were subjected to GO biofunctional annotation and KEGG pathway enrichment analysis using the DAVID database. A mouse model of HUA was constructed using potassium oxyzate combined with high purine diet, and the effects of SZ on these mice were examined using ELISA and biochemical index detection. RESULTS Network pharmacological analysis identified 11 major bioactive substances in SZ and 72 potential targets involved in the treatment of hyperuricemia, involving multiple biological processes and different signaling pathways. It was shown that SZ significantly reduced serum uric acid, creatinine and urea nitrogen levels in hyperuricemic mice by inhibiting XOD activity.SZ also reduced the levels of urate transporter protein 1 (URAT1) while increasing the levels of ATP-binding cassette transporter protein subfamily G member 2 (ABCG2).RNA sequencing analysis revealed that the levels of uric acid in the model group vs. treated group, control group vs. model group and 112, 536 and 107 differentially expressed genes (DEGs) in the control vs. treated groups, respectively. qRT-PCR results indicated that SZ downregulated the expression of genes related to Th17 cell differentiation as well as mRNA of genes on IL-17 and PI3K/Akt signaling pathways. CONCLUSION SZ has a therapeutic effects on hyperuricemia. The mechanism of action may be related to the inhibition of hepatic XOD activity, down-regulation of URAT1 levels, up-regulation of ABCG2 levels, affecting the differentiation of Th17 cells and thus the IL-17 signaling pathway, thereby reducing the inflammatory response. |
| Key words: hyperuricemia SZ network pharmacology rna-seq traditional Chinese medicine |
