摘要
目的探索阿尔茨海默病（Alzheimer’sdisease，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Illumina／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（nfimics）、抑制剂（inhibitor），转染至SH—SY5Y细胞系中，采用Westernblot法检测细胞中β-淀粉样前体蛋白裂解酶1（BACEl）的表达。结果与正常对照组（contr01）相比，AD组血清中miR-146a-5p（10g2AD／Control=2．3）、miR-195—5p（10g2AD／Con-trol=10．2）、miR-20b-5p（10g，AD／Control=15．1）表达上调，miR-19b-3p（10g2AD／Control=-8．0）、miR-125b-3p（10g，AD／Control=-153）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BACEl蛋白表达减少，抑制剂组BACEl蛋白表达增加。结论nliR-19b-3p可能通过调节BACEl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 Illumi- na/Solexa high-throughput sequencing technique. The miRNA lentiviral plasmids were constructed and injec- ted 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 13-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 （ log2AD/Control = 10.2 ）, miR-20b-5p（ logzAD/Control = 15.1 ） in serum of AD group was up-regulated and the expression of miR-19b- 3p（ log2AD/Control = - 8.0 ） and miR-125b-3p （ log2AD/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 ex- pression of BACE1 in miR-19b-3p mimetic group was decreased and the protein expression of BACE1 in in- hibitor group was increased. Conclusion miR-19b-3p may improve the cognitive function of AD patients via regulating the expression of BACE1.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2017年第11期994-998,共5页
Chinese Journal of Behavioral Medicine and Brain Science
基金
浙江省自然科学基金项目（LY13H250001）
杭州市科技计划项目（20130633831）
