雷欢;邓琴;刘子源;张维;徐凌云;

• 1:武汉轻工大学生命科学与技术学院

摘要(Abstract)：

目的 基于网络药理学和分子对接的方法，探讨香叶木素治疗高尿酸血症肾病（HN）的分子机制。方法 运用中药系统药理学平台（TCMSP）、SwissTargetPrediction数据库、ChEMBL数据库筛选香叶木素的作用靶点基因，借助GeneCards、DisGeNET数据库检索HN疾病靶点基因，运用Venny 2.1在线工具获取香叶木素与HN的共有靶点基因；基于STRING数据库构建共有靶点基因的蛋白质—蛋白质相互作用关系（PPI）网络，通过Cystoscape软件进行可视化分析，拓扑学分析筛选核心靶点基因；借助DAVID数据库对共有靶点基因进行GO功能注释和KEGG通路富集分析。以核心靶点基因编码的蛋白为受体、香叶木素为配体，采用AutoDock Vina 1.1. 2软件进行分子对接验证。结果 共挖掘出香叶木素潜在作用靶点基因150个、HN相关靶点基因443个，两者共有靶点基因22个。共有靶点基因的PPI网络共包含节点22个、边85条；筛选得到核心靶点基因8个，包括TP53、XDH、ESR1、ABCG2等。富集分析共得到GO功能条目82个，其中生物过程51个（涉及尿酸代谢等）、细胞组成13个（涉及细胞质等）、分子功能18个（涉及跨膜转运蛋白活性等）；共富集到35个KEGG信号通路，包括TP53信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路、肿瘤坏死因子（TNF）信号通路、核因子κB(NF-κB)信号通路等。分子对接结果表明，香叶木素与TP53等8个核心靶点基因编码蛋白的结合能均低于-5 kcal/mol，有较强的结合活性。结论 香叶木素可能是通过作用于TP53、XDH、ESR1、ABCG2等核心靶点基因，进而调控TP53信号通路、PI3K/Akt信号通路、TNF信号通路、NF-κB信号通路等多条通路发挥对HN的治疗作用。

关键词(KeyWords)： 香叶木素;高尿酸血症肾病;网络药理学;分子对接;分子机制

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 雷欢;邓琴;刘子源;张维;徐凌云;

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