基于生物信息学方法对抑郁小鼠长期服用氟西汀后差异基因表达的分析

Expression of hippocampal different genes in depressed mice after long-term use of fluoxetine by bioinformatic analysis

目的以GEO数据库中GSE6476系列芯片数据为分析对象,结合生物信息学方法分析氟西汀长期作用下抑郁小鼠海马相关基因的表达情况。方法利用R语言与Bioconductor、DAVID、STRING、Uniprot等方法对差异基因进行了筛选和分析。结果得到144个差异基因,其中上调基因111个,下调基因33个(log FC>1,P<0.05)。经GO分析发现这些差异基因中有14个参与生物过程(BP),16个参与细胞组成(CC),9个参与分子功能(MF)。Pathway通路分析发现,差异基因主要集中在甘油酯代谢、N-聚糖的生物合成、精氨酸和脯氨酸代谢途径、花生四烯酸代谢、甘油磷脂代谢、氧化磷酸化等通路,进一步分析,78个差异基因的蛋白产物间存在相互作用,并筛选到Vim、Bdnf、Npy、Gfap、Penk、Fosb、Cd44、Timp1、Lgals1等核心基因,这些基因在神经肽信号通路、女性妊娠、树突和神经发育等生物功能中充当了重要的角色。结论氟西汀长期作用前后抑郁小鼠海马基因表达有较大差异性,通过核心基因的筛选为揭示抑郁症的基因靶向治疗指导提供了重要的理论基础。

Objective To investigate the expression of hippocampal different genes in depressed mice after chronical use of fluoxetine based on microarray data GSE6476（ the Gene Expression Omnibus accession number） from Gene Expression Omnibus（ GEO） database and bioinformatics analysis. Methods Depended on R Bioconductor,DAVID,STRING and Uniprot,differential genes were found and analyzed. Results Totally 144 differential genes were screened out,in which 111 were up-regulated genes and 33 were downregulated genes（ log FC 1,P〈0. 05）. Gene ontology（ GO） function analysis showed that 14 differentially expressed genes were involved in the biological process（ BP）,16 genes were involved in the celluar component（ CC）,and 9 genes existed in the molecular function（ MF）. Pathway analysis revealed that the target genes were mainly involved in the progression of glycerolipid metabolism,Nglycan biosynthesis,arginine and proline metabolism,arachidonic acid metabolism,glycerophospholipid metabolism and oxidative phosphorylation. The protein products of 78 differential genes had constructed the interacting network. In those genes,Vim,Bdnf,Npy,Gfap,Penk,Fosb,Cd44,Timp1,Lgals1 were core genes that exert significant roles in neuropeptide signaling pathway,female pregnancy,dendrite and nerve development（ log FC〉1）. Conclusion The study demonstrates that hippocampal gene expression in the depressed mice is significantly different after the long-term effects of fluoxetine,and the screening of core genes provides an important theoretical foundation in the guidance of gene targeting therapy for depression.