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目的 探索阿尔茨海默病(Alzheimer’s disease,AD)患者血清差异表达的miRNAs及其与认知功能的关系.方法 采用lllumina/Solexa高通量测序技术分析AD患者和健康体检老年人两组(各30例)血清miRNA表达谱;构建miRNA慢病毒质粒,注射至造模成功的AD大鼠静脉内,采用水迷宫实验分析大鼠的认知功能;合成miRNA模拟剂(mimics)、抑制剂(inhibitor),转染至SH-SY5Y细胞系中,采用Western blot法检测细胞中β-淀粉样前体蛋白裂解酶1(BACE1)的表达.结果 与正常对照组(control)相比,AD组血清中miR-146a-5p(log2 AD/Control=2.3)、miR-195-5p(log2 AD/Control=10.2)、miR-20b-5p(log2AD/Control=15.1)表达上调,miR-19b-3p(log2AD/Control =-8.0)、miR-125b-3p(log2AD/Control=-15.3)表达下调,差异有统计学意义(P＜ 0.05);与AD组[(26.50±3.12)s]相比,AD+miR-19b-3p组[(15.33± 2.78)s]的大鼠逃避潜伏期明显缩短,差异具有统计学意义(P＜0.05);与正常对照相比,miR-19b-3p模拟剂组BACE1蛋白表达减少,抑制剂组BACE1蛋白表达增加.结论 miR-19b-3p可能通过调节BACE1的表达改善AD患者的认知功能.“,”Objective To explore the relationship between differentially expressed miR-19b-3p and cognitive function in patients with Alzheimer’s disease (AD).Methods The miRNA expression profiles of patients with AD(AD group,n=30) or healthy elderly people (NC group,n=30) were analyzed by Illumina/Solexa high-throughput sequencing technique.The miRNA lentiviral plasmids were constructed and injected into the model of AD rats.The cognitive function of rats was analyzed with water maze test.The mimics and inhibitors were synthesized and transfected into SH-SY5Y cell lines.The protein expression of β-amyloid precursor protein cleavage enzyme 1 (BACE1) was detected by western blot.Results Compared with the NC group,the expression of miR-146a-5p (log2AD/Control =2.3),miR-195-5p (log2 AD/Control =10.2),miR-20b-5p(log2AD/Control =15.1) in serum of AD group was up-regulated and the expression of miR-19b-3p (log2 AD/Control =-8.0) and miR-125b-3p (log2 AD/Control =-15.3) was down-regulated (P＜ 0.05).Compared with the rats in the AD group((26.50±3.12) s),the rats in the AD+miR-19b-3p group ((15.33±2.78) s) showed significantly shorter escape latencies(P＜0.05).Compared with the NC group,the protein expression of BACE1 in miR-19b-3p mimetic group was decreased and the protein expression of BACE1 in inhibitor group was increased.Conclusion miR-19b-3p may improve the cognitive function of AD patients via regulating the expression of BACE1.