快速老化相关miRNAs在遗忘型轻度认知功能障碍患者血清中的表达及其生物信息学分析

摘要

Objective:To explore the expressions of miRNAs related to accelerating senescence in serum of the patients with amnestic mild cognitive impairment (aMCI), and to clarify their effects in the pathogenesis of aMIC.Methods:The levels of miRNAs related to accelerating senescence (miR-132, miR-193b, miR-130b, miR-20a, miR-296, miR-329 and miR-206) were measured in the serum of the patients with aMCI (aMCI group,n=66) and healthy controls(control group,n=76) using quantitative real-time PCR(qRT-PCR).The genes targeted by the altered miRNAs were predicted by TargetScan 6.0.DAVID was used to analyze the function of miRNA target genes.The serum levels of brain derived neurotrophic factor (BDNF) and silent in formation regulator 1(SIRT1) were measured by enzyme-linked immunosorbent assay (ELISA) method.Results:The expression levels of miR-206 and miR-132 in serum of the patients in aMCI group were significantly higher than those in control group (P<0.05).BDNF and SIRT1 were both target genes of miR-206 and miR-132.The levels of BDNF (29.50 μg·L-1± 3.13 μg·L-1) and SIRT1 (1.86 μg·L-1± 0.25 μg·L-1) in serum of the patients in aMCI group were both obviously lower than those in control group (BDNF: 32.29 μg·L-1±3.66 μg·L-1;SIRT1: 2.10 μg·L-1± 0.29 μg·L-1, P<0.05).Conclusion:The expression levels of miR-206 and miR-132 in serum of the aMCI patients are significantly up-regulated.Both of them might be involved in the pathogenesis of aMCI through inhibiting the BDNF and SIRT1 expressions.%目的: 探讨快速老化相关miRNAs在遗忘型轻度认知功能障碍(aMCI) 患者血清中的表达,阐明其在aMCI发病中的作用.方法: 选取aMCI患者(aMCI组, n=66)和认知功能正常老年人(对照组, n=76)为研究对象.采用实时定量PCR技术(qRT-PCR)检测2组受试者血清中miR-132、miR-193b、miR-130b、miR-20a、miR-296、miR-329和miR-206的表达.采用TargetScan 6.0软件对差异表达的血清miRNAs进行靶基因预测,并通过DAVID在线工具分析靶基因生物学功能;利用酶联免疫吸附实验(ELISA)检测2组受试者血清中靶基因的水平.结果: aMCI组患者血清miR-206和miR-132表达水平均明显高于对照组(P<0.05),其他miRNAs则差异无统计学意义(P>0.05).靶基因预测,脑源性神经营养因子(BDNF)和沉默信息调节因子1(SIRT1)共为miR-206和miR-132的靶基因.aMCI组患者血清BDNF和SIRT1表达水平均明显低于对照组(BDNF:29.50 μg·L-1±3.13 μg·L-1 vs 32.29 μg·L-1±3.66 μg·L-1;SIRT1:1.86 μg·L-1±0.25 μg·L-1 vs2.10 μg·L-1± 0.29 μg·L-1),2组比较差异均有统计学意义(P<0.05).结论: miR-206和miR-132在aMCI患者血清中表达水平明显升高,二者可能通过调控其靶基因BDNF和SIRT1的表达参与aMCI发病过程.