首页|NGR1改善糖尿病肾病炎症反应的靶点分析及验证

NGR1改善糖尿病肾病炎症反应的靶点分析及验证

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为阐明壮药三七特征皂苷(NGR1)的抗炎特性及其保护肾足细胞的作用,本文运用网络药理学和分子对接技术,探究NGR1改善糖尿病肾病(DN)炎症分子机制及其潜在靶点。Swiss Target Prediction数据库检索NGR1的靶点;OMIM和Gene Cards数据库检索DN炎症反应的相关基因;构建交集靶点的蛋白质-蛋白质相互作用(PPI)网络;运用Metascape进行GO和KEGG富集分析。利用Autodock Vina对交集靶点-NGR1进行分子对接,GRAMM-X评估交集靶点-NLRP3炎症小体的亲和力。采用MPC-5细胞进行体外实验验证。结果表明,STAT3、VEGFA为NGR1主要靶点,均与NLRP3密切关联。NGR1干预DN炎症反应主要涉及PI3K/Akt等信号通路。NGR1降低P-STAT3、VEGFA、NLRP3的表达水平。结果提示,NGR1通过降低STAT3磷酸化水平干预NLRP3的激活、调控VEGFA的表达,改善DN炎症反应。
Target proteins analysis and validation of NGR1 on inflammatory response in Diabetic nephropathy
This study aimed to investigate the molecular mechanism and potential targets of Zhuang Medicine Panax-Notoginseng NGR1 on the inflammatory response in Diabetic nephropathy(DN).Targets of NGR1 were found by the Swiss Target Prediction database.Genes related to inflammatory response in DN were re-trieved from OMIM and Gene Cards databases.A protein-protein interaction(PPI)network between the above intersection targets was constructed.GO and KEGG pathway enrichment analysis was conducted,fol-lowed by molecular docking analysis of NGR1 with its targets by using Autodock Vina.The affinity between NGR1-targets related to the inflammatory response in DN and NLRP3 inflammasome was evaluated by GRAMM-X.MPC-5 cells were used for in vitro detection.The results showed that STAT3 and VEGFA were the main targets of NGR1,which were closely related to NLRP3.PI3K/Akt signaling pathway,etc.was involved in NGR1 protection against DN.Cell experiments showed that NGR1 reduced the expression levels of P-STAT3,VEGFA and NLRP3.The results suggest that NGR1 interfered with the activation of NLRP3,regulated the expression of VEGFA and then prevented DN,through lower-down the phosphorylation level of STAT3.

Notoginsenoside R1NLRP3 inflammasomeDiabetic nephropathyNetwork pharmacologyMolecular docking

任祥亭、吕建珍、刘秋霞、黄国东、王志静、李统宇、陆世龙、LOO Wei-Yin

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广西中医药大学药学院,南宁 530200

广西中医药大学基础医学院,南宁 530200

广西国际壮医医院,南宁 530021

广西中医药大学第一附属医院,南宁 530023

广西中医药大学瑞康医院,南宁 530011

广西中医药大学国际教育学院,南宁 530001

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三七皂苷R1 NLRP3炎症小体 糖尿病肾病 网络药理学 分子对接

广西自然科学基金面上项目广西自然科学基金面上项目广西科技基地和人才专项

2020GXNSFAA1590702022GXNSFAA035608桂科AD20297142

2024

四川大学学报(自然科学版)
四川大学

四川大学学报(自然科学版)

CSTPCD北大核心
影响因子:0.358
ISSN:0490-6756
年,卷(期):2024.61(3)