目的 通过网络药理学方法探究黄精水提物（PKAE）抗高尿酸血症（HUA）的药效物质基础及作用机制。方法 基于网络药理学，通过中药系统药理学数据库与分析平台（TCMSP）预测黄精活性成分的作用靶点，运用GeneCards和OMIM数据库检索与HUA相关的疾病靶点。采用Cytoscape 3.6.2构建拓扑图，利用DAVID平台对黄精治疗HUA的靶点进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析。运用AutoDockTool（1.5.6）软件进行分子对接，预测主要化合物与关键靶点的结合度。通过ip氧嗪酸钾建立小鼠HUA模型，设对照组、模型组、别嘌呤醇（40 mg·kg_-1）组、苯溴马隆（20 mg·kg_-1）组及PKAE高、低剂量（15.6、7.8 g·kg_-1）组，以PKAE进行干预，并且检测血清中尿酸、肌酐值。结果 网络药理学筛选的核心靶点4个，分别为JUN、TNF、TP53、PPARG，对应活性成分为黄芩素、β-谷甾醇、薯蓣皂苷元、异甘草素等。KEGG通路分析提示PKAE可能通过丝裂原活化蛋白激酶（MAPK）、核因子-κB（NF-κB）、白细胞介素（IL）-17、血管内皮生长因子（VEGF）等信号通路发挥治疗作用，PPARG可能为其关键靶点。药效实验表明，与模型组比较，PKAE高、低剂量组都能显著（P＜0.05）降低小鼠血清中尿酸与肌酐的含量。结论 黄精可通过多种活性成分（如芹菜素、黄芩素、β-谷甾醇等）作用于PPARG等靶点，调控NF-κB、肿瘤坏死因子-α（TNF-α）、丝裂原活化蛋白激酶（MAPK）等炎症和代谢相关通路，降低尿酸和肌酐水平，从而发挥抗HUA作用。

Objective The method of network pharmacology was used to explore the material basis and mechanism of Polygonatum kingianum (PKAE) against hyperuricemia. Methods Based on network pharmacology, the target of active components of P. kingianum was predicted by TCMSP database, and the disease targets related to hyperuricemia were searched by GeneCards and OMIM database. Cytoscape3.6.2 was used to construct the topology map, and GO enrichment analysis and KEGG pathway analysis were carried out on the target of P. kingianum in the treatment of hyperuricemia by DAVID platform. The molecular docking was carried out by AutoDockTool (1.5.6) software to predict the binding degree between the main compounds and the key targets. The mouse HUA model was established by intraperitoneal injection of potassium oxazinate. The mice were divided into blank group, model group, allopurinol (40 mg·kg^-1) group, benzbromarone (20 mg·kg^-1) group, high and low dose (15.6, 7.8 g·kg^-1) PKAE groups. PKAE was used to intervene, and the values of uric acid (UA) and creatinine (Cr) in serum were measured. Results The four core targets screened by network pharmacology were JUN, TNF, TP53 and PPARG, respectively, and the corresponding active components were baicalein, β-sitosterol, diosgenin, isoglycyrrhizin and so on. It is predicted that the main pathways of PKAE in the treatment of hyperuricemia were MAPK signal pathway, NF-κB signal pathway, IL-17 signal pathway, vascular endothelial growth factor signal pathway and so on. It is predicted that PPARG is the main target of PKAE in the treatment of hyperuricemia. Through the efficacy experiment, compared with the model group, PKAE high and low dose group can significantly reduce the contents of Cr and UA in serum of mice. Conclusion PKAE can reduce serum UA and creatinine in hyperuricemic mice. Its active components may be apigenin, baicalein, β-sitosterol, diosgenin, isoliquiritigenin. Its mechanism may be to inhibit the inflammatory molecular pathways such as NF-κB and TNF-α, activate the target of PPARG protein, inhibit the expression of MAPK signal pathway, reduce the value of UA and creatinine in blood, and reduce the inflammatory reaction caused by UA, reduce the inflammatory reaction caused by UA and achieve the purpose of treating hyperuricemia.

R285.5

贵州省科技计划项目（黔科合基础-ZK[2022]一般389；黔科合支撑[2023]一般046；黔科合支撑[2020]4Y104；黔科合基础-ZK[2023]一般310）；贵州省科技创新基地（黔科合中引地〔2023〕 003）；贵州省高层次创新型人才百层次人才（黔科合平台人才-GCC〔2023〕 048）