雷公藤多苷与呋塞米联用治疗肾病综合征人体内相互作用机制的网络药理学通路预测

Herb-drug interaction mechanism of Tripterygium glycosides and Furosemide in the treatment of nephrotic syndrome based on network pharmacology

[目的]通过网络药理学方法预测雷公藤多苷(TG)主要成分与呋塞米联用在治疗肾病综合征方面的作用通路,以探究药物人体内相互作用的机制。[方法]通过在多个数据库检索TG的主要成分、两药对应人体作用靶点、肾病综合征相关靶点,进行药物与靶点间分子对接。绘制蛋白与蛋白相互作用(PPI)网络图、靶点-组织分布网络图、化合物-靶点网络图、化合物-靶点-通路网络图,分析两药作用机制异同和可能存在的相互作用。[结果]TG主要讨论成分14种,TG人体肾病综合征潜在靶点136个,呋塞米81个。TG覆盖呋塞米70个潜在靶点。两药共同的主要组织分布可能包含有肝、骨髓、全血、平滑肌、肺、全脑、脑桥、扁桃体、心肌细胞、T细胞、B细胞等。分子对接验证显示TG药物与靶点的结合活性优于呋塞米。两药通过作用于靶点共同干预人体细胞凋亡、血小板活化及其他27条可能的信号通路。[结论]TG与呋塞米在治疗肾病综合征方面存在人体内药物相互作用,共同作用于人体多个靶点,通过干预多条信号通路影响疾病治疗。

[Objective]To study the mechanism of the interaction between the main components of tripterygium glycosides(TG)and furosemide in the treatment of nephrotic syndrome(NS)by network pharmacology.[Methods]The main components of TG,the two drug’s NS-related human targets were searched in multiple databases.Molecular docking between drugs and targets was performed.Protein-protein interaction(PPI)network maps,target-tissue distribution network maps,compound-target network maps,compound-target-path network maps was mapped,and the similarities and differences and possible interactions between the two drugs was analysed.[Results]There were 14 main components of TG,136 human NS targets of TG and 81 of furosemide.TG covers 70 targets of furosemide.The main tissues shared by the two drugs are liver,bone marrow,whole blood,smooth muscle,lung,whole brain,pons,tonsils,cardiomyocytes,T cells,B cells,and the like.The binding activity of the TG drug to the target is better than furosemide.The two drugs intervene in human apoptosis,platelet activation and other 27 signaling pathways through targeted sites.[Conclusion]TG and furosemide have drug interactions in the treatment of NS,which act on multiple targets of the human body and affect the treatment of diseases by intervening multiple signaling pathways.