基于生物信息学和网络药理学探讨补肾健脾方改善2型糖尿病作用机制
Exploration on the Mechanism of Bushen Jianpi Prescription in Improving Type 2 Diabetes Mellitus Based on Bioinformatics and Network Pharmacology
邓钰骅 1封杰妮 1朱娴琼 1徐颖 1黄宇轩 2刘继洪3
作者信息
- 1. 广州中医药大学,广东 广州 511000
- 2. 广东药科大学,广东 广州 511400
- 3. 佛山市中医院,广东 佛山 528000
- 折叠
摘要
目的 基于生物信息学和网络药理学探讨补肾健脾方治疗2型糖尿病(T2DM)的作用机制.方法 通过TCMSP、BATMAN-TCM数据库筛选补肾健脾方活性成分及作用靶点,通过GEO数据库获取T2DM相关数据集GSE18732和GSE19420,通过Mfuzz分析筛选与糖尿病同步变化的基因,作为T2DM疾病靶点.获取补肾健脾方与T2DM疾病靶点交集靶点,作为补肾健脾方治疗T2DM的作用靶点,通过STRING数据库构建靶点蛋白相互作用网络,筛选网络中的关键靶点,通过GO功能和KEGG通路富集分析其生物功能,对关键靶点进行单因素Logistic回归,筛选Hub基因,基于Hub基因构建T2DM预测模型.结果 获取补肾健脾方药物靶点1 837个,T2DM疾病靶点983个,药物-疾病交集靶点115个,主要富集于内分泌抵抗、胰岛素抵抗、胰岛素信号通路、非酒精性脂肪性肝病、细胞凋亡、细胞衰老、AMPK信号通路、糖尿病并发症中的AGE-RAGE信号通路和HIF-1信号通路.Hub基因有NFKB1和SREBF1,预测模型曲线下面积=0.829,具有良好的预测性能.结论 本研究综合生物信息学和网络药理学研究发现,补肾健脾方可能通过调控AMPK通路和AGE-RAGE等通路,发挥延缓T2DM进展作用,但仍需进一步实验验证.
Abstract
Objective To explore the mechanism of Bushen Jianpi Prescription for the treatment of type 2 diabetes mellitus(T2DM)based on bioinformatics and network pharmacology.Methods The active components and action targets of Bushen Jianpi Prescription were screened through TCMSP and BATMAN-TCM databases.T2DM-related datasets GSE18732 and GSE19420 were obtained by GEO database,and genes with synchronous changes with diabetes were screened by Mfuzz analysis as disease targets of T2DM.The intersection targets between Bushen Jianpi Prescription and the T2DM disease targets were obtained,as the therapeutic targets of Bushen Jianpi Prescription for the treatment of T2DM.The protein-protein interaction network of the targets was constructed by STRING database,and the key targets in the network were screened.Enrichment analysis of its biological functions was performed through GO and KEGG pathway enrichment.Single factor Logistic regression was used for screening Hub genes,and construct a T2DM prediction model based on Hub genes.Results Totally 1 837 drug targets of Bushen Jianpi Prescription were obtained,with 983 T2DM disease targets,and 115 drug-disease intersection targets,mainly enriched in endocrine resistance,insulin resistance,insulin signaling pathway,non-alcoholic fatty liver disease,apoptosis,cellular senescence,AMPK signaling pathway,AGE-RAGE signaling pathway and HIF-1 signaling pathway.The Hub genes include NFKB1 and SREBF1,with a prediction model curve area of 0.829 and had good predictive performance.Conclusion This study integrates the bioinformatics and network pharmacology findings,suggesting that Bushen Jianpi Prescription may regulate AMPK pathway and AGE-RAGE pathway through NFKB1 and SREBF1,etc.,to achieve the effect of delaying T2DM progression,but further experimental confirmation is needed.
关键词
2型糖尿病/补肾健脾方/网络药理学/生物信息学Key words
type 2 diabetes mellitus/Bushen Jianpi Prescription/network pharmacology/bioinformatics引用本文复制引用
基金项目
佛山市社会科学基金规划项目(2022-QN23)
佛山市社会科学基金规划项目(2022-GJ160)
出版年
2024
国家科技期刊平台
NSTL
万方数据