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Cytoscape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,Amphetamine 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。
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 glutamate receptor signaling pathway,chemical synaptic transmission,etc.KEGG signaling pathways of intersection target were mainly Cocaine 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.
作者
赵丽
李福智
甄露露
王宏烨
于简瑞
钟家旺
郭笑川
侯阳
Zhao Li;Li Fuzhi;Zhen Lulu;Wang Hongye;Yu Jianrui;Zhong Jiawang;Guo Xiaochuan;Hou Yang(The Third Clinical Medical College,Jinzhou Medical University,Jinzhou 121000 China;Tongliao People′s Hospital,Tongliao 028000 China;The First Clinical Medical College,Jinzhou Medical University;Institute of Life Sciences,Jinzhou Medical University,Jinzhou 121000 China)
出处
《锦州医科大学学报》
CAS
2024年第2期40-44,50,共6页
Journal of Jinzhou Medical University
基金
辽宁省级2022年大学生创新创业计划项目,项目编号:S202210160022
辽宁省教育厅重点攻关项目,项目编号:LJKZZ20220095
锦州市指导性科技计划项目,项目编号:JZ2023B044。
