NGR1改善糖尿病肾病炎症反应的靶点分析及验证
Target proteins analysis and validation of NGR1 on inflammatory response in Diabetic nephropathy
任祥亭 1吕建珍 1刘秋霞 2黄国东 3王志静 4李统宇 3陆世龙 5LOO Wei-Yin6
作者信息
- 1. 广西中医药大学药学院,南宁 530200
- 2. 广西中医药大学基础医学院,南宁 530200
- 3. 广西国际壮医医院,南宁 530021
- 4. 广西中医药大学第一附属医院,南宁 530023
- 5. 广西中医药大学瑞康医院,南宁 530011
- 6. 广西中医药大学国际教育学院,南宁 530001
- 折叠
摘要
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.
Abstract
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.
关键词
三七皂苷R1/NLRP3炎症小体/糖尿病肾病/网络药理学/分子对接Key words
Notoginsenoside R1/NLRP3 inflammasome/Diabetic nephropathy/Network pharmacology/Molecular docking引用本文复制引用
基金项目
广西自然科学基金面上项目(2020GXNSFAA159070)
广西自然科学基金面上项目(2022GXNSFAA035608)
广西科技基地和人才专项(桂科AD20297142)
出版年
2024
国家科技期刊平台
NSTL
万方数据