摘要
目的 应用网络药理学的研究方法预测二甲双胍/多奈哌齐治疗糖尿病脑病的作用机制并初步进行动物实验.方法 Drugbank和DisGeNET数据库检索二甲双胍/多奈哌齐和糖尿病脑病靶点,得到交集靶点.使用String数据库和Cyto-scape软件构建蛋白互作网络(PPI),DAVID数据库对交集靶点进行功能(gene ontology,GO)和通路(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,筛选出关键基因,动物实验进行初步验证.结果 药物和疾病共同靶点15 个、10个hub基因;GO功能注释结果显示:交集靶点主要富集于离子型谷氨酸受体信号通路、化学突触传递等.KEGG通路富集分析表明交集靶点的KEGG信号通路主要为Cocaine addiction、Nicotine addiction等.动物实验结果显示,二甲双胍/多奈哌齐能改善糖尿病学习认知能力,改善脑组织 IL1B 和 ACHE 的改变.结论 可通过调节 GRIN2B、GRIN2A、GRIN1、GRIN2C、GRIN2D、GRIN3A、NOS1、GRIN3B、IL1B、ACHE等靶点基因,调控 Cocaine addiction,Nicotine addiction,Am-phetamine addiction,cAMP signaling pathway等信号通路来实现抗糖尿病脑病作用,并初步验证.
Abstract
Objective To predict the mechanism of action of metformin/donepezil in the treatment of diabetic encephalopathy by using the method of network pharmacology.Methods The targets of metformin/donepezil were searched through Drugbank database.DisGeNET database was used to search the targets of diabetic encephalopathy,and the intersection targets of drug targets and disease targets were obtained.String database and Cytoscape software were used to construct protein Interaction network(PPI),and DAVID database was used to conduct functional(GO)and pathway(KEGG)enrichment analysis for intersection targets,and key genes were selected for preliminary verification in animal experiments.Results There were 15 common targets of drugs and diseases.Ten hub genes were obtained.GO functional annotation results showed that the intersection targets were mainly enriched in ionotropic gluta-mate receptor signaling pathway,chemical synaptic transmission,etc.KEGG signaling pathways of intersection target were mainly Co-caine addiction,Nicotine addiction,etc.Animal experiments showed that metformin/Donepezil can improve diabetic learning and cognitive ability,and improve the changes of IL1B and ACHE in brain tissue.Conclusion By regulating GRIN2B,GRIN2A,GRIN1,GRIN2C,GRIN2D,GRIN3A,NOS1,GRIN3B,IL1B,ACHE and other target genes,Regulation of Cocaine addiction,Nicotine addiction,Amphetamine addiction,cAMP signaling pathway,etc.,to achieve the anti-diabetic encephalopathy effect,and preliminary verification
基金项目
辽宁省省级大学生创新创业训练计划(2022)(S202210160022)
辽宁省教育厅重点攻关项目(LJKZZ20220095)
锦州市指导性科技计划(JZ2023B044)
NETL
NSTL
万方数据