基于网络药理学的黄芪-当归-川芎治疗糖尿病肾脏疾病机制研究

A study on mechanism of Astragalus-Angelica sinensis and Ligusticum wallichii in treating diabetic kidney disease based on network pharmacology

目的:利用网络药理学技术研究黄芪-当归-川芎治疗糖尿病肾脏疾病(Diabetic Kidney Disease,DKD)的潜在作用机制。方法:运用网络数据库对三味药物黄芪、当归、川芎组成的药组的化学成分及其作用靶点与DKD的靶点进行筛选。利用Cytoscape 3.7.2软件,构建“中药组活性成分-作用靶点”网络。利用STRING数据库构建黄芪-当归-川芎与DKD的蛋白相互作用网络图(Protein-protein Interaction Network Graph,PPI),通过拓扑分析得到核心靶点。最后对黄芪-当归-川芎与DKD的交集靶点进行生物通路及富集分析,验证此药组对DKD的治疗作用。结果:黄芪-当归-川芎包括29个有效成分,对应靶点142个,核心靶点15个;主要生物学过程及通路包括蛋白多糖在癌症中的作用、流体剪切应力与动脉粥样硬化、HIF-1信号通路、疟疾、癌症途径等,其中聚集在流体剪切应力与动脉粥样硬化的靶点最多。结论:黄芪-当归-川芎药组治疗DKD的机制是多种生物学过程共同作用,可能主要通过改变血流剪切力对肾脏血管的正调控来实现治疗目的,也提示该通路是未来研究治疗DKD的重要方向。

Objective:Using network pharmacology technology to study the potential mechanism of Astragalus-Angelica sinensis and Ligusticum wallichii(黄芪-当归-川芎)on diabetic kidney disease(DKD).Methods:The drug combination’s chemical composition,the action targets of three herbal medicine(astragalus,angelica and Ligusticum wallichit)and the targets of DKD were screened by network database.The network of TCM medicine’s active ingredient-action target was constructed by using the software Cytoscape 3.7.2.The protein-protein interaction network(PPI)of astragalus-angelica-chuanxiong and DKD was constructed by using STRING database,and the core targets were found through topological analysis.Finally,biological pathway and enrichment analysis were carried out on Astragalus-Angelica sinensis and Ligusticum wallichii and DKD’s intersection targets.Results:Astragalus-Angelica sinensis and Ligusticum wallichii 29 active ingredients and 519 corresponding targets,core targets.The main biological processes and pathways included:Fluid shear stress and atherosclerosis、HIF-1 signaling pathway、Malaria、Pathways in cancer、Proteoglycans in cancer and so on.Excepting the cancer pathway,among which the most targets were aggregated in Fluid shear stress and atherosclerosis.Conclusion:The mechanism of drug combination Astragalus-Angelica sinensis and Ligusticum wallichii to cure for DKD was worked together through multiple biological processes.It was possible to realize the therapeutic purpose mainly through blood flow shearing force to put the Positive regulation on renal vessels.It also suggested that this pathway was an important direction for the treatment of DKD’s study in the future.