基于网络药理学研究芪血通络片治疗糖尿病周围神经病变的作用机制

Study on the mechanism of the Qixue Tongluo tablets in treating diabetes peripheral neuropathy based on network pharmacology

目的:利用网络药理学技术研究芪血通络片治疗糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、国家中医药百科全书数据库(ETCM)筛选芪血通络片中涉及的九种中药信息;利用人类基因数据库(GeneCards)搜索DPN的相关靶点信息,将二者取交集得到成药-疾病交集靶点,制作韦恩图;使用String平台构建交集靶点蛋白质-蛋白质相互作用网络,将蛋白质-蛋白质相互作用网络TSV文件导入Cytoscape 3.7.1软件,运用Cytoscape 3.7.1软件进行关键靶点分析;根据度值进行二次建模,进行亮暗颜色分析,从而检测出最关键的核心靶点;此外利用Metascape数据库分析药物-疾病靶点互作网络,完成对基因本体论(GO)和京都基因与基因组百科全书(KEGG)的信息的富集与分析,从而检测出芪血通络片治疗糖尿病周围神经病变的活性物质成分。结果:获得药物潜在靶点282个,疾病潜在靶点1247个,二者交集靶点109个,筛选后的核心靶点有β-连环蛋白(Catenin Beta 1,CTNNB1)等;GO功能富集分析获得细胞生物学过程包括:活性氧代谢过程等;KEGG通路富集分析获得细胞对氮化合物的反应信号通路等。结论:通过网络药理学分析,芪血通络片在治疗糖尿病周围神经病变的过程中,可通过多靶点、多基因、多通路进行表达。此药除了具有降血糖降血脂作用,还具有营养神经,减轻血管内皮损害,延缓动脉粥样硬化,预防癌症的效果。

Objective:To study the mechanism of the Qixue Tongluo tablets(芪血通络片)in the treatment of diabetic peripheral neuropathy(DPN)by using network pharmacology technology.Methods:Nine kinds of TCM medicine information and potential pharmacological effects and target information in the Qixue Tongluo tablets were screened through TCMSP and ETCM.Using GeneCards to search for the relevant target information of DPN,the two were intersected to obtain the drug-disease intersection target,and the Venn diagram was made.The String platform was used to construct the intersection target PPI network.The PPI network TSV file was imported into Cytoscape 3.7.1 software,and the key targets were analyzed by Cytoscape 3.7.1 software.Secondary modeling was performed according to the degree value,and bright and dark color analysis was performed to detect the most critical core targets.In addition,the Metascape database was used to analyze the drug disease target interaction network to complete the enrichment and analysis of GO and KEGG information,so as to detect the active substance components of the Qixue Tongluo tablets in the treatment of diabetes peripheral neuropathy.Results:A total of 282 potential targets for drugs and 1247 potential targets for diseases were obtained,and 109 targets were intersected.The core targets after screening:CTNNB1,etc..GO functional enrichment analysis obtained cell biological processes including reactive oxygen species metabolism,etc..KEGG pathway enrichment analysis obtained VEGFA signaling pathway,etc..Conclusion:By network pharmacology analysis,the Qixue Tongluo tablets can be expressed through multiple targets,multiple genes and multiple pathways in the treatment of diabetic peripheral neuropathy to reduce vascular endothelial damage,delay atherosclerosis,and prevent cancer.