目的 基于网络药理学、分子对接和体内外高尿酸模型实验探讨筒鞘蛇菰治疗高尿酸血症（HUA）的作用，阐明其活性成分的主要作用靶点和信号通路相关机制。 方法 通过台湾中医药资料库、本草组鉴数据库、化学专业数据库、TargetNet数据库、SwissTargetPrediction数据库、GeneCards数据库、药物靶点数据库（TTD）、DrugBank数据库、DisGeNET数据库、人类在线孟德尔遗传（OMIM）数据库和Venny数据库获取筒鞘蛇菰治疗HUA的潜在靶点；利用STRING数据库和Cytoscape软件构建筒鞘蛇菰活性成分-预测靶点网络和蛋白-蛋白互作（PPI）网络，并进行拓扑分析筛选筒鞘蛇菰主要活性成分和核心靶点，采用R软件进行基因本体论（GO）功能和京都基因组与基因百科全书（KEGG）信号通路富集分析，采用AutoDock Vina软件进行分子对接验证。NRK-52E细胞分为空白对照组、空白给药组、模型组和不同浓度（2.0、10.0及50.0 μmol·L^－1）圣草酚（EDT）组，模型组和不同浓度EDT组细胞采用腺苷诱导制备高尿酸细胞模型，采用高效液相色谱（HPLC）法检测各组细胞培养上清液中尿酸（UA）水平。雄性ICR小鼠随机分为空白对照组、空白给药组、模型组和EDT组，后2组小鼠制备HUA模型，采用试剂盒检测各组小鼠血清中UA、肌酐（Cr）和血尿素氮（BUN）水平；取小鼠两侧肾组织，称质量，计算各组小鼠肾脏指数；TUNEL染色法观察各组小鼠肾组织中细胞凋亡情况；Western blotting法检测各组小鼠肾组织中蛋白激酶B（AKT）、磷酸化蛋白激酶B（p-AKT）、磷脂酰肌醇3-激酶（PI3K）、磷酸化磷脂酰肌醇3-激酶（p-PI3K）、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）和基质金属蛋白酶9（MMP-9）蛋白表达水平。 结果 筛选得到筒鞘蛇菰6种活性成分，涉及116个交集靶点，14个核心靶点。富集分析得到1 828个GO条目和145条信号通路。分子对接结果，EDT与MMP-9具有较好的结合活性。高尿酸细胞实验，与空白对照组比较，模型组细胞中UA水平明显升高（P<0.01）；与模型组比较，2.0、10.0和50.0 μmol·L^－1 EDT组细胞中UA水平明显降低（P<0.01）。与空白对照组比较，模型组小鼠血清中UA、Cr和BUN水平及肾脏指数明显升高（P<0.01）；与模型组比较，EDT组小鼠血清中UA、Cr和BUN水平及肾脏指数明显降低（P<0.05或P<0.01）。与空白对照组比较，模型组小鼠肾组织中可见大量凋亡细胞；与模型组比较，EDT组小鼠肾组织中凋亡细胞数明显减少。与空白对照组比较，模型组小鼠肾组织中p-AKT/AKT及p-PI3K/PI3K比值和Bcl-2蛋白表达水平明显降低（P<0.05或P<0.01），Bax和MMP-9蛋白表达水平明显升高（P<0.01）；与模型组比较，EDT组小鼠肾组织中p-AKT/AKT及p-PI3K/PI3K比值和Bcl-2蛋白表达水平明显升高（P<0.05或P<0.01），Bax和MMP-9蛋白表达水平明显降低（P<0.01）。 结论 筒鞘蛇菰活性成分EDT具有降UA作用，且可能通过激活PI3K/AKT信号通路抑制细胞凋亡并缓解肾损伤。

Objective To investigate the efficacy of Balanophora involucrata Hook.f. in treatment of hyperuricemia （HUA） based on network pharmacology， molecular docking， and hyperuricemia models in vivo and in vitro，and to clarify the main targets of its active components and related signaling pathway mechanism. Methods The potential targets of Balanophora involucrata Hook.f. in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan， the Chinese Herbal Medicine Identification Database，Professional Chemical Database， TargetNet Database， SwissTargetPrediction Database， GeneCards， Therapeutic Target Database （TTD），DrugBank Database， DisGeNET Database， Online Mendelian Inheritance in Man （OMIM） Database， and Venny Database. STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction （PPI） network for Balanophora involucrata Hook.f.；topological analysis was used to select the main active components and core targets；Gene Ontology （GO） functional and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed by R software； AutoDock Vina software was used for molecular docking validation. The NRK-52E cells were divided into blank control group， blank administration group， model group， and different concentrations （2.0， 10.0， and 50.0 μmol·L^-1） of erythrodiol （EDT） groups. High-performance liquid chromatography culture （HPLC） was used to detect the uric acid （UA） levels in the cell culture supernatants in various groups. The male ICR mice were divided into blank control group， blank administration group， model group， and EDT group； the mice in the last two groups were used to prepare the HUA models； kits were used to detect the levels of UA， creatinine （Cr）， and blood urea nitrogen （BUN） in serum of the mice in various groups；the bilateral kidney tissue of the mice was harvested and weighed； the kidney indexes of the mice in various groups were calculated；TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups；Western blotting method was used to detect the expression levels of protein kinase B （AKT），phosphorylated AKT （p-AKT），phosphoinositide 3-kinase （PI3K），phosphorylated PI3K（p-PI3K）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and matrix metalloproteinase-9 （MMP-9） proteins in kidney tissue of the mice in various groups. Results Six active components of Balanophora involucrata Hook.f.were identified， involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways. The molecular docking results showed that EDT had good binding activity with MMP-9. The high uric acid cell experiment results showed that compared with blank control group， the UA level in the cells in model group was significantly increased （P<0.01）； compared with model group， the UA levels in the cells in 2.0， 10.0， and 50.0 μmol·L^-1 EDT groups were significantly decreased （P<0.01）. Compared with blank control group， the levels of UA， Cr， and BUN in serum of the mice in model group were increased（P<0.01）， and the kidney indexes were significantly increased （P<0.01）； compared with model group， the levels of UA， Cr， and BUN in serum of the mice in EDT group were decreased （P<0.05 or P<0.01），and the kidney index was significantly decreased （P<0.05 or P<0.01）. Compared with blank control group， the number of apoptotic cells in kidney tissue of the mice in model group was increased； compared with model group， the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased. Compared with blank control group， the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased （P<0.05 or P<0.01）， while the expression levels of Bax and MMP-9 proteins were significantly increased （P<0.01）； compared with model group， the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased （P<0.05 or P<0.01）， and the expression levels of Bax and MMP-9 proteins were significantly decreased （P<0.01）. Conclusion The active component of Balanophora involucrata Hook.f.，EDT，has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.