目的 基于网络药理学和分子对接技术探讨补肾活血方治疗尿酸性肾病（uric acid nephropathy， UAN）的分子作用机制。方法 采用中药系统药理学数据库TCMSP筛选出补肾活血方的有效活性成分。通过PubChem、DrugBank、SymMap和SwissTargetPrediction数据库筛选出中药各成分作用靶点。借助GeneCards、DisGenet、malaCards和OMIN数据库获取尿酸性肾病的靶点基因。David绘图工具筛选出中药与疾病的交集靶点，利用Cytoscape3.9.0软件构建“中药-活性成分-疾病-靶点”网络关系图，并通过CytoNCA插件构建蛋白质相互作用网络（PPI），筛选得到核心靶点蛋白。采用AutoDock Vina 1.1.2软件将补肾活血方关键有效成分和核心靶点进行分子对接。最后运用乙胺丁醇和腺嘌呤诱导的尿酸性肾病模型对网络药理学预测的结果进行基础实验验证。结果 本研究共筛选得到补肾活血方治疗UAN的作用靶点234个，其中核心靶点19个，对应5种中药的113种有效成分。GO富集分析共得到925条基因功能信息，KEGG富集分析发现112条信号通路，涉及Toll样受体、NF-κB、PI3K-Akt、p53、TNF等信号通路治疗尿酸性肾病。分子对接结果显示，双脱甲氧基姜黄素、异黄酮等关键活性成分与ALB、MMP9、TLR4等关键核心靶点有较好的结合活性。动物实验结果显示，与模型组相比，补肾活血方组、非布司他组大鼠肾组织TLR4和NF-κB蛋白表达量和血清MMP-9水平明显降低（P<0.05）；血清ALB水平明升高（P<0.05）。结论 本研究提示，补肾活血方中关键活性成分可能通过抑制TLR4/NF-κB信号通路降低TLR4、NF-κB和MMP-9水平，减轻炎症反应，进而减少ALB漏出，发挥保护肾脏治疗尿酸性肾病的作用。

Objective Based on network pharmacology and molecular docking technology to explore the molecular mechanism of Bushen Huoxue Decoction in the treatment of uric acid nephropathy (UAN).Methods The effective active ingredients of Bushen Huoxue Recipe were screened out by TCMSP, a pharmacology database of Chinese medicine system. Through the PubChem, DrugBank, SymMap and SwissTargetPrediction database, the target of each component of traditional Chinese medicine was screened. The target genes of uric acid nephropathy were obtained with the help of GeneCards, DisGenet, malaCards and OMIN databases. Get the target genes of uric acid nephropathy with the help of GeneCards and DisGenet databases. Drawing tool David screened out the intersection targets, and used Cytoscape 3.9.0 software to construct a network relationship of "Traditional Chinese Medicine-Active Ingredients-Disease-Target". Construct a protein interaction (PPI) network relationship through String database and Cytoscape 3.9.0 software. AutoDock Vina 1.1.2 software was used to molecularly dock the key active ingredients of Bushen Huoxue Recipe and the core target. Finally, the uric acid nephropathy model induced by ethambutol and adenine was used to verify the results of network pharmacology prediction.Results In this study, a total of 234 targets of Shenhuoxue Recipe for treating UAN were screened, including 19 core targets, corresponding to 113 active ingredients in 5 Chinese medicines. GO enrichment analysis obtained a total of 925 gene function information. KEGG enrichment analysis found 112 signal pathways, involving Toll-like receptor signal pathway, NF-κB signal pathway, PI3K-Akt signal pathway, p53 signal pathway, TNF signal pathway, etc. The results of molecular docking showed that key active ingredients such as didemethoxy curcumin and isoflavones had good binding activity with key core targets such as ALB, MMP9, and TLR4. The results of animal experiments showed that compared with the model group, the kidney tissue TLR4 and NF-κB protein expressions and the serum MMP-9 levels of the rats in the Bushen Huoxue Recipe group and the febuxostat group were significantly decreased (P<0.05); Serum ALB level was increased (P<0.05).Conclusion This study suggests that the key active ingredients in Bushen Huoxue Recipe may reduce the levels of TLR4, NF-κB and MMP-9 by inhibiting the TLR4/NF-κB signaling pathway, thereby reducing the inflammatory response, thereby reducing the leakage of ALB, and playing the role of protecting the kidneys in the treatment of uric acid.

河南省中医管理局河南省中医药科学研究专项（2018ZY2001）：基于“肾虚血瘀-炎症微环境关联”假说/TLR4-MyD88-NF-kB信号通路探讨补肾活血方干预尿酸性肾病的机制研究，负责人：邓伟；河南省科学技术厅科技攻关项目（182102311173）：基于大数据挖掘中老年高尿酸血症及尿酸性肾病健康风险因素的评估及控制研究，负责人：邓伟；郑州市科技局普通科技攻关项目（20150320）：基于Toll样受体4信号通路运用补肾活血法治疗尿酸性肾病炎症机制研究，负责人：邓伟。