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| 基于网络药理学、分子对接和动物实验探究芪蛭痛风颗粒治疗高尿酸血症的作用机制 |
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罗铃潇1, 张明珠2, 吴亭彧1, 胡思娜1, 包乌吉斯古冷3, 孙鲁英1,2
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1.北京中医药大学东直门医院, 北京 100700;2.北京中医药大学房山医院, 北京 102400;3.中国中医科学院西苑医院, 北京 100091
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| 摘要: |
| [目的] 结合网络药理学、分子对接和动物实验，探究芪蛭痛风颗粒（QZTF）治疗高尿酸血症（HUA）的潜在活性成分和作用机制。[方法] 通过中药系统药理学数据库（TCMSP）和成分靶点预测平台Swiss Target Prediction筛选QTZF活性成分和有效靶点，使用DrugBank、OMIM、GeneCards、DisGeNET等数据库进行HUA疾病靶点筛选，取交集靶点使用STRING数据库构建蛋白质相互作用（PPI）网络，进行基因本体（GO）及京都基因与基因组百科全书（KEGG）富集分析，研究QZTF治疗HUA的可能作用机制，并运用分子对接技术进行验证。构建氧嗪酸钾行腹腔注射的HUA大鼠模型，采用酶联免疫（ELISA）法检测血清尿酸、肌酐、尿素氮及肝脏黄嘌呤氧化酶（XOD）活性，实时荧光定量PCR（qPCR）法检测肾脏尿酸盐阴离子转运体1（URAT1）mRNA和葡萄糖转运体9（GLUT9）mRNA的表达。[结果] 网络药理学结果表明，QZTF的可能活性成分有1101个，交集靶点有182个，核心靶点有信号转导和转录激活因子3（STAT-3）、肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、Jun原癌基因（JUN）、白细胞介素-1β（IL-1β）、细胞凋亡调节因子2（BCL-2）、甘油醛-3-磷酸脱氢酶（GAPDH）、核因子Kappa B亚基1（NF-κB1）、半胱氨酸天冬氨酸蛋白酶3（Caspase-3）、Toll样受体4（TLR4）。分子对接结果表明主要活性成分与靶点结合活性良好。动物实验结果表明，QZTF可有效降低HUA大鼠的血清尿酸水平（P<0.001），抑制肝脏XOD活性（P<0.05），qPCR结果表明HUA大鼠肾脏URAT1和GLUT9的mRNA的表达显著下降（P<0.01）。[结论] QZTF可以通过多成分、多靶点、多通路的途径发挥治疗HUA的作用。 |
| 关键词: 高尿酸血症 芪蛭痛风颗粒 网络药理学 分子对接 尿酸转运蛋白 炎症 |
| DOI：10.11656/j.issn.1673-9043.2026.08.09 |
| 分类号:R285.5 |
| 基金项目:北京医药健康协同中医药高质量研发工程项目（ZYYGZL-2025-036）；首都卫生发展科研专项项目（2022-2-7074）；北京中医药大学新教师启动基金项目（2024-BUCMX JKY009）。 |
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| Exploring the mechanism of Qizhi Tongfeng Granules in the treatment of hyperuricemia using network pharmacology，molecular docking，and animal experiments |
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LUO Lingxiao1, ZHANG Mingzhu2, WU Tingyu1, HU Sina1, BAO Wujisiguleng3, SUN Luying1,2
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1.Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;2.Fangshan Hospital, Beijing University of Chinese Medicine, Beijing 102400, China;3.Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
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| Abstract: |
| [Objective] To explore the potential active ingredients and mechanism of QiZhi TongFeng Granules （QZTF）in the treatment of hyperuricemia（HUA）by integrating network pharmacology，molecular docking，and animal experiments. [Methods] The active ingredients and effective targets of QTZF were screened through the Traditional Chinese Medicine Systems Pharmacology（TCMSP） database and the component target prediction platform Swiss Target Prediction，while hyperuricemia disease targets were obtained from DrugBank，OMIM， GeneCards，and DisGeNET databases. The intersection targets were selected，and the STRING database was used to construct the protein-protein interaction（PPI）network for gene ontology（GO）and Kyoto encyclopedia of genes and genomes（KEGG）enrichment analysis. Molecular docking was used to study the potential mechanism of QZTF in the treatment of HUA. The rat model of HUA was established by intraperitoneal injection of potassium oxyazinate. Serum uric acid，creatinine，urea nitrogen，and liver xanthine oxidase（XOD）activity were detected by enzyme linked immunosorbent assay（ELISA），and the expressions of glucose transporter 9（GLUT9）mRNA and urate transporter 1（URAT1）mRNA in the kidneys were detected by real-time fluorescence quantitative PCR（qPCR）. [Results] The network pharmacology results indicated that there were 1101 possible active components of QZTF， 182 intersection targets，and the core targets included signal transducer and activator of transcription 3（STAT-3）， tumor necrosis factor（TNF），interleukin 6（IL6），Jun protooncogene，（JUN），interleukin 1β（IL1β），Bcell lymphoma-2（BCL-2），glyceraldehyde-3-phosphate dehydrogenase（GAPDH），nuclear factor kappa-B1（NF-κB1）， cysteine aspartate protease 3（Caspase-3），toll-like receptor 4（TLR4）. The results of molecular docking showed that the main active ingredients had good docking activity with the targets. The results of animal experiments showed that QZTF could effectively reduce the serum uric acid level of HUA rats and inhibit the XOD activity in the liver. The qPCR results indicated that the mRNA expressions of URAT1 and GLUT9 in the kidneys of HUA rats decreased significantly. [Conclusion] QZTF can exert therapeutic effects on HUA through multi-component，multitarget，and multi-pathway pathways. |
| Key words: hyperuricemia QiZhi TongFeng Granules network pharmacology molecular docking uric acid transporter inflammation |
