【摘要】 目的分析D-半乳糖联合Al Cl3诱导阿尔茨海默病(AD)与野生型小鼠海马microRNAs(miRNAs)表达差异。方法昆明种小鼠,随机分成AD模型组和野生型对照组,AD模型组每日腹腔注射D-半乳糖90 mg/kg和Al Cl340 mg/kg溶液,野生型对照组腹腔注射等量的生理盐水,1次/d,连续90 d。物体识别实验测试各组小鼠识别、记忆能力。miRNA芯片检测各组小鼠海马miRNAs的表达,并进行后续的生物信息学分析。结果在物体识别实验中,AD模型组小鼠探索新物体所用的时间较野生型对照组减少(P<0.01),分辨指数(8.97±1.33)较野生型对照组(34.42±3.74)减低(P<0.001)。在3批次AD模型组和野生型对照组间均有显著变化的17个miRNAs(≥2.0倍上调或下调)的预测靶基因重点分布在AD相关信号通路、神经营养因子信号通路、长时程增强效应相关通路,并处于这些信号通路的关键位置。结论 17个差异表达的miRNAs可能通过调节相关信号通路关键细胞因子的表达,参与AD的进程。更多还原

【Abstract】 Objective To analyze differentially expressed miRNAs in D-galactose joint almuinim chloride（ Al Cl3） induced AD with wild-type mice hippocampus. Methods Kunming mice were randomly divided into AD model and wild type control groups,the model group was treated with D-galactose 90 mg·kg^-1·d^-1and Al Cl340 mg·kg^-1·d^-1solution（ i. p.）,the control group was injection of normal saline（ i. p.） once a day for 90 d. Object recognition test was used to test object recognition preference. The miRNA microarray was used to detect miRNAs expression in mice hippocampus of each group. Results In the object recognition test,AD model mice showed quite less exploration time on new object（ P<0. 01） and significant lower discrimination index（ P<0. 001） compared with that of control group. Microarray analysis identified 17 differentially expressed miRNAs（ ≥2. 0 fold up and down regulated,intersection of three sets）. DAVID Functional Annotation Cluster（ FAC） and pathway analysis of the target genes of miRNAs revealed confident enrichment scores for AD associated signaling pathway,neurotrophin signaling pathway and long-term potentiation pathway. Conclusions Bioinformatic analysis of the differentially expressed miRNAs have identified a number of miRNAs with putative involvement in AD development process.更多还原