基于网络药理学与分子对接技术探讨保肾灵丸治疗糖尿病肾病的机制

Network pharmacology and molecular docking technology reveal the mechanism of kidney-protecting spirit pill in the treatment of diabetic nephropathy

目的:基于系统网络药理学与分子对接技术探讨保肾灵丸治疗糖尿病肾病(DN)的作用机制。方法:查询中药药理学数据库获取保肾灵丸活性成分及作用靶点,与疾病靶点取交集。对交集靶点进行蛋白质互作(protein-protein interaction,PPI)网络构建,并进行GO和KEGG富集分析,得到关键靶点和小分子进行分子对接验证。结果:共预测到活性成分60个及治疗DN靶点112个。关键成分为香芹甾醇、3,9-二-O-甲基尼索林、香芹酚、棕榈苷A和16α-羟基脱氢曲霉醇酸,尤其是香芹甾醇、棕榈苷A和16α-羟基脱氢曲霉醇酸。关键靶点为PIK3CA、MAPK1、AKT1、PIK3R1、BCL2等,与多种癌症相关通路及糖尿病并发症中的AGE-RAGE信号通路、内分泌抵抗、脂质与动脉粥样硬化等通路密切相关。结论:保肾灵丸治疗DN的作用机制具有多成分、多靶点、多通路的特点,各中药之间有协同作用,为保肾灵丸药理作用研究提供依据。

Objective:To explore the mechanism of kidney-protecting spirit pill for the treatment of diabetic nephropathy(DN)based on the network pharmacology and molecular docking technology.Methods:The database of TCMSP and Swiss Target Prediction was searched to obtain the active ingredients and targets of kidney-protecting spirit pill,and the intersection with the disease targets was obtained.The protein-protein interaction(PPI)network of intersection targets was constructed,GO and KEGG enrichment were analyzed.The key targets and small molecules were obtained and their interactions were verified by molecular docking.Results:A total of 60 active ingredients and 112 therapeutic DN targets were predicted.The key components were Cerevisterol,3,9-di-O-methylnissolin,Jaranol,Palmidin A and 16α-Hydroxydehydrotrametenolic acid.The key targets were PIK3CA,MAPK1,AKT1,PIK3R1 and BCL2,which were closely related to cancer-related pathways,AGE-RAGE signaling pathway,endocrine resistance,lipids and atherosclerosis pathways in diabetic complications.Conclusion:The mechanism of kidney-protecting spirit pill in the treatment of DN is characterized by multi-components,multi-targets and multi-pathways,with synergistic effects between the herbs,which provides a basis for the study of the pharmacological effects of kidney-protecting spirit pill.