摘要
目的通过网络药理学方法研究二甲双胍治疗糖尿病视网膜病变(DR)的分子药效机制。方法自Pubchem数据库获取二甲双胍的化学结构,通过PharmMapper、SwissTargetPrediction及DrugBank数据库获取药物作用的靶点基因;通过GeneCards和DisGeNET获取数据库内DR的致病基因。取二甲双胍的作用靶点基因与DR致病基因的交集,将交集内的基因作为二甲双胍治疗DR的目标基因。通过STRING数据库构建目标基因的蛋白-蛋白互作网络。通过Metascape对目标基因进行生物本体论和功能通路分析。结果获取了31个二甲双胍治疗DR的目标基因。这些基因的生物学过程主要富集于对缺氧的反应及核苷酸代谢等;细胞组件主要富集于微绒毛、细胞紧密连接等;分子功能主要富集于辅助因子结合、一氧化氮合成酶(NOS)活性等;功能通路富集于止血、血管内皮生长因子(VEGF)信号通路等。结论二甲双胍主要通过影响细胞之间紧密连接、细胞缺氧反应、NOS以及VEGF信号通路等控制DR的进展。
Objective To explore the pharmacological molecular mechanisms of metformin against diabetic retinopathy(DR)based on network pharmacology approach.Methods After chemical constitution of metformin was acquired from Pubchem database,target genes of metformin were identified by PharmMapper,SwissTargetPrediction and DrugBank database,and the pathological genes were obtained from GeneCards and DisGeNET database.Subsequently,the intersection of metformin targets and pathologic targets of DR were served as therapeutic targets of metformin against DR.The construction of protein-protein interaction(PPI)network was constructed by STRING,gene ontology(GO)and functional pathway were analyzed by Metascape.Results Overall 31 therapeutic target genes of metformin against DR were obtained.Biological process of the PPI network was mainly enriched in reactive oxygen species metabolic process and nucleotide metabolism;cellular component was mainly enriched in microvillus and adherens junction;molecular function was mainly enriched in cofactor binding and nitric oxide synthase(NOS)activity.Functional pathway was mainly enriched in hemostasis and signaling by vascular endothelial growth factor(VEGF).Conclusions Metformin prevents the development of DR mainly through affecting cellular tight junctions and reaction to hypoxia,modulating NOS and VEGF signaling pathways.
作者
陈源
邢茜
黄正如
Chen Yuan;Xing Qian;Huang Zhengru(Department of Ophthalmology,Changshu No.2 People's Hospital,Changshu 215500,China)
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2020年第12期1011-1015,共5页
Chinese Journal Of Experimental Ophthalmology
基金
江苏省卫计委医学科研课题面上项目(H2017001)
苏州市科技发展计划项目(SYSD2019017)
常熟市卫健委科技发展计划项目(cswsq201907)。
