基于网络药理学和分子对接探讨白藜芦醇预防妊娠高血压的作用机制

To investigate the mechanism of resveratrol in preventing hypertension during pregnancy based on network pharmacology and molecular docking

目的通过网络药理学和分子对接技术预测白藜芦醇预防妊娠高血压的作用机制。方法利用Pharm Mapper、TCMSP和Swiss Target Prediction数据库获得白藜芦醇相关靶点。妊娠高血压相关靶点在GeneCards、DisGeNET和OMIM数据库中检索。利用Cytoscape3.7.1软件构建“白藜芦醇-妊娠高血压-信号”的关联网络。核心靶点通过DAVID进行GO和KEGG分析。运用Autodock软件对关键靶点与白藜芦进行分子对接。结果筛选出白藜芦醇与妊娠高血压85个交集靶点,排名前10的靶点依次为IL-6、VEGFA、TP53、EGFR、ESR1、CASP3、PTGS2、STAT3、CTNNB1、PPARG。10个核心靶点蛋白与白藜芦醇的结合良好。富集显著性较高的通路主要有脂质与动脉粥样硬化、蛋白聚糖肿瘤通路、流体剪切应力和动脉粥样硬化、内分泌抵抗、糖尿病并发症中的AGE-RAGE信号通路等。结论白藜芦醇可能通过调控IL-6、VEGFA和EGFR等关键基因,从而干预AGE-RAGE和内分泌抵抗信号传递途径,实现对妊娠高血压的预防作用。

Objective To predict the mechanism of resveratrol in preventing gestational hypertension by network pharmacology and molecular docking.Methods Pharm Mapper,TCMSP and Swiss Target Prediction database were used to obtaine the resveratrol related targets.Targets associated with gestational hypertension were retrieved from GeneCards,Dis-GeNET and OMIM databases.The association network of“Resveratrol-gestational hypertension-signaling”was constructed using Cytoscape3.7.1 software.Core targets were analyzed by GO and KEGG by DAVID.Autodock software was used for molecular docking of key targets and resveratrol.Results 85 intersection targets of resveratrol and gestational hypertension were selected,and the top 10 targets were IL-6,VEGFA,TP53,EGFR,ESR1,CASP3,PTGS2,STAT3,CTNNB1 and PPARG.The 10 core target proteins were well bound to resveratrol.The pathways with high enrichment were mainly lipid and atherosclerosis,proteoglycan tumor pathway,fluid shear stress and AGE-RAGE signaling pathway in atherosclerosis,endocrine resistance,diabetes complications,etc.Conclusion Resveratrol may regulate key genes such as IL-6,VEGFA and EGFR,thereby interfering with AGE-RAGE and endocrine resistance signaling pathway to achieve the prevention of hypertension in pregnancy.