基于网络药理学与分子对接探讨渴络欣胶囊“异病同治”治疗糖尿病微血管并发症的作用机制  

The action mechanism of the Keluoxin capsules on diabetic microvascular complications from the theory treating different diseases by the same therapy based on network pharmacology and molecular docking

作　　者：范晓旭 姜斯佳 华姞安 冯颖童 沈奕玮 王祯[1] 王景霞[1] FAN Xiaoxu

机构地区：[1]北京中医药大学,北京100029

出　　处：《中医临床研究》2024年第26期1-8,共8页Clinical Journal Of Chinese Medicine

基　　金：国家自然科学基金(82074036)。

摘　　要：目的:基于网络药理学与分子对接探讨渴络欣胶囊“异病同治”治疗糖尿病微血管并发症的潜在机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM数据库检索药物的化合物成分及靶点,利用GeneCards、NCBI、OMIM和DisGeNET数据库筛选疾病靶点,绘制韦恩图并取药物-疾病交集靶点。采用String数据库构建蛋白质-蛋白质相互作用网络,使用Cytoscape 3.8.0软件构建“药物-成分-靶点-疾病-通路”网络。采用R 4.1.2软件及微生信平台进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。利用AutoDock Vina和Pymol软件对关键活性成分和核心靶点进行分子对接和可视化处理。结果:共获得药物靶点350个、糖尿病微血管并发症靶点2259个,两者的交集靶点为186个;拓扑分析结果表明,丝氨酸/苏氨酸蛋白激酶1、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-6、磷酸甘油醛脱氢酶等靶点度值较大;GO富集分析共获得2973个条目,KEGG信号通路有180条;分子对接结果显示,关键活性成分与核心靶点具有良好的结合能力。结论:渴络欣胶囊可通过多成分、多靶点、多通路治疗糖尿病微血管并发症,其机制可能与有效成分通过磷脂酰肌醇3激酶-蛋白激酶B、晚期糖基化终末产物-晚期糖基化终末产物受体、缺氧诱导因子-1和TNF等通路发挥抗炎、抗氧化应激、调控新生血管生成等“异病同治”作用有关。Objective:To investigate the potential action mechanism of the Keluoxin capsules(渴络欣胶囊)in the treatment of diabetic microvascular complications from the theory treating different diseases by the same therapy based on network pharmacology and molecular docking.Methods:TCMSP and Batman-TCM database were used to obtain the compound components and targets of the medicines,and GeneCards,NCBI,OMIM,and DisGeNET databases were used to identify the targets associated with the disease.The Venny diagram was drew to obtain the intersecting targets of medicines and diseases.String database was used to construct a protein-protein interaction network.Cytoscape 3.8.0 software was used to construct a medicine-component-target-disease-pathway network.GO and KEGG enrichment analyses were performed using R 4.1.2 software and the bioinformatics platform.Molecular docking and visualization for key active ingredients and core targets were performed by AutoDock Vina and Pymol software.Results:A total of 350 medicines targets and 2259 diabetic microvascular complication targets were obtained.There were 186 medicine-disease intersecting targets.The results of topological analysis showed that the targets of AKT1,TNF,IL-6,and GAPDH had larger degree values.A total of 2973 items were obtained by GO enrichment analysis,and 180 KEGG signaling pathways were obtained.Molecular docking results showed that the key active ingredients had good binding capacity with the core targets.Conclusion:The Keluoxin capsules can play a role in the treatment of diabetic microvascular complications through multi-component,multi-target,and multi-pathway,and its action mechanism may be related to the role of treating different diseases by the same therapy of active ingredients in anti-inflammatory,anti-oxidative stress and regulation of neo-angiogenesis through PI3K-Akt,AGE-RAGE,HIF-1,TNF pathways.

关 键 词：渴络欣胶囊 糖尿病微血管并发症 异病同治 网络药理学 作用机制 

分 类 号：R25[医药卫生—中医内科学]