基于网络药理学与分子对接技术探讨丹红注射液治疗糖尿病肾病的作用机制  

The action mechanism of the Danhong injection on diabetic nephropathy based on network pharmacology and molecular docking technology

作　　者：陈正义 张浩岚 王澄槟 谢锦楠 王若涵 肖晓燕 綦雪巍 CHEN Zhengyi

机构地区：[1]广州中医药大学深圳临床医学院,广东深圳518116 [2]广州中医药大学针灸康复临床医学院,广东广州510405 [3]广州中医药大学护理学院,广东广州510405 [4]深圳市龙岗中心医院,广东深圳518116

出　　处：《中医临床研究》2024年第29期93-99,共7页Clinical Journal Of Chinese Medicine

基　　金：广州中医药大学省级大学生创新创业训练计划项目(202310572092)。

摘　　要：目的:基于网络药理学和分子对接技术探讨丹红注射液治疗糖尿病肾病可能的作用靶点及相关分子机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集丹红注射液的有效成分及其靶点,从GeneCards数据库中检索糖尿病肾病靶点,将疾病靶点与丹红注射液有效成分靶点取交集,获得丹红注射液治疗糖尿病肾病的潜在作用靶点。应用Cytoscape 3.9.1软件构建中药-活性成分-疾病靶点可视化网络,并分析网络节点度值以筛选关键的有效成分。通过蛋白质-蛋白质相互作用网络分析得到丹红注射液治疗糖尿病肾病的关键蛋白靶点,利用David数据库对丹红注射液治疗糖尿病肾病的潜在靶点进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制。借助AutoDockTools 1.5.6软件进行分子对接,分析关键的有效成分与蛋白靶点的相互作用关系。结果:共收集丹红注射液有效成分84个,其治疗糖尿病肾病的潜在靶点有195个。蛋白质-蛋白质相互作用网络分析显示,肿瘤蛋白p53(Tumor Protein p53,TP53)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、信号转导和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6等为丹红注射液治疗糖尿病肾病的关键靶点。KEGG富集分析涉及糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)信号通路、IL-17信号通路、TNF信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-Kinase,PI3K)-蛋白激酶B(Akt)信号通路及缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)信号通路等。分子对接显示,丹红注射液主要的有效活性成分与关键靶点分子TP53、AKT1、STAT3能够自发结合,其中丹参酮ⅡObjective:To investigate potential targets and associated molecular mechanisms of the Danhong injection(丹红注射液)in the management of diabetic nephropathy(DN)utilizing network pharmacology and molecular docking technology.Methods:The active constituents and their respective targets of the Danhong injection were acquired from the TCMSP,while targets associated with DN were retrieved from the GeneCards database.The potential targets of the Danhong injection in the treatment of DN was obtained by intersecting the disease targets with the active component targets of the Danhong injection.Cytoscape 3.9.1 software was employed to construct a visual network depicting the relationship between Chinese medicine,active ingredients,and disease targets.A node degree analysis was conducted to identify key active ingredients.Key protein targets of the Danhong injection on DN were identified through protein-protein interaction network analysis.Utilizing the David database,GO function analysis and KEGG pathway enrichment analysis on potential targets of the Danhong injection in the treatment of DN were performed to predict the action mechanism.AutoDockTools 1.5.6 software was utilized for molecular docking to examine the interaction between key active components and protein targets.Results:A total of 84 active constituents of the Danhong injection were compiled,and 195 potential targets associated with the treatment of DN were identified.The protein-protein interaction network analysis revealed TP53,AKT1,STAT3,TNF,and IL-6 as key targets of the Danhong injection in the treatment of DN.The KEGG enrichment analysis implicated pathways such as AGE-RAGE signaling pathway in diabetic complication,IL-17 signaling pathway TNF signaling pathway,PI3K-Akt signaling pathway,and HIF-1 signaling pathway.The molecular docking analysis demonstrated that the principal active components of the Danhong injection could spontaneously bind to key target molecules such as TP53,AKT1,and STAT3,with tanshinone IIA exhibiting the highest binding af

关 键 词：糖尿病肾病 丹红注射液 网络药理学 分子对接 

分 类 号：R256.5[医药卫生—中医内科学]