目的:分析慢性应激抑郁模型大鼠海马组织miRNA表达特征，探究与抑郁发作相关的差异表达miRNA。方法:将12只SPF级雄性SD大鼠按随机数字表法分为对照组和模型组，每组6只。对照组大鼠群养，正常饮水摄食，不给任何刺激。模型组大鼠孤养，并给予8种不可预知的慢性应激刺激28 d，建立大鼠抑郁模型。利用旷场实验检测大鼠的抑郁行为，运用miRNA 4.0 Array芯片技术筛选出对照组和模型组大鼠海马间差异表达miRNA，利用Fisher精确检验，筛选出具有显著性差异的miRNA，采用miRanda和TargetScan两个数据库对显著性差异miRNA分别进行靶基因预测，取两种预测结果的交集，对差异表达miRNA利用GO数据库进行基因功能注释，KEGG数据库进行信号通路(Pathway)注释。结果:miRNA芯片技术分析结果显示，与对照组比较，模型组大鼠海马组织中得到25条差异表达miRNA，其中上调的miRNA有15条(n P1.3)，下调的miRNA有10条(n P1.3)。这些miRNA的靶基因主要参与细胞内信号转导、RNA聚合酶Ⅱ启动子转录的调节、DNA模板化、蛋白质磷酸化、大脑发育、心脏发育等生物学进程(n P<0.01)。Pathway分析显示，轴突导向和癌症通路的显著性水平最为显著，其次是AMPK信号通路、cGMP-PKG信号通路、神经营养信号通路等抑郁发作的经典信号通路(n P<0.05)。n 结论:慢性应激抑郁模型大鼠海马miRNA表达谱发生明显改变，差异表达的25条miRNA主要参与了轴突导向、神经营养信号通路等抑郁发作密切相关的信号通路及癌症通路。“,”Objective:To analyze the expression characteristics of miRNA in the hippocampus of rats with chronic unpredictable mild stress, and to explore the differentially expressed miRNA associated with depressive episodes.Methods:Twelve SPF male SD rats were randomly divided into control group and model group, with 6 in each group. The rats in the control group were raised in groups, drank water and fed normally without giving any stimulation. Rats in the model group were all orphaned and subjected to 8 kinds of chronic unpredictable mild stress for 28 days. Open field experiment was used to detect the depressive behavior of rats.The miRNA 4.0 Array chip technology was used to screen the differentially expressed miRNA in hippocampus of rats in the two groups, and the target genes were predicted through miRanda and TargetScan databases, and the differentially expressed miRNA were analyzed for target gene function and KEGG signal pathway.Results:miRNA microarray analysis showed that compared with the control group, 25 differentially expressed miRNA were obtained in the hippocampus of model group, including 15 up-regulated miRNA (n P1.3) and 10 down-regulated miRNA (n P1.3). The target genes of these miRNA were mainly involved in biological processes such as intracellular signal transduction, RNA polymerase II promoter transcription regulation, DNA templating, protein phosphorylation, brain development, and heart development(n P<0.01). Pathway analysis showed that the significance level of axon guidance and cancer pathways were the most significant, followed by AMPK signaling pathway, cGMP-PKG signaling pathway, neurotrophic signaling pathway and other classic signaling pathways for depression(n P<0.05).n Conclusion:The expression profile of miRNA in hippocampus of chronic stress depression model rats is significantly changed. The 25 miRNA differentially expressed are mainly involved in axon guidance, neurotrophic signaling pathways and other signaling pathways closely related to depression episodes, as well as cancer pathways.