血浆hsa-let-7d-3p在阿尔茨海默病中的诊断价值及功能  

Diagnostic Value and Function of Plasma hsa-let-7d-3p in Alzheimer′s Disease

作　　者：赵超 陈丹 王暖 周昊 陈国芳[2] ZHAO Chao;CHEN Dan;WANG Nuan;ZHOU Hao;CHEN Guofang(Department of Neurology,Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University/Xuzhou No.1 People′s Hospital of,Xuzhou 221000,China;Department of Neurology,Xuzhou Central Hospital,Xuzhou 221000,China)

机构地区：[1]徐州医科大学附属徐州市立医院/徐州市第一人民医院神经内科,江苏徐州221000 [2]徐州市中心医院神经内科,江苏徐州221000

出　　处：《医学综述》2023年第20期4346-4352,共7页Medical Recapitulate

摘　　要：目的探索hsa-let-7d-3p在阿尔茨海默病(AD)中的诊断价值和功能。方法收集2018年4月至2022年3月于徐州市第一人民医院就诊的80例AD患者作为AD组,同期招募60名健康者作为健康对照组。筛选GSE46579和GSE120584数据集中AD患者血浆中显著变化的微RNA(miRNA),采集两个数据集中上调及下调的miRNA进行生物标志物的筛选。通过实时定量反转录聚合酶链反应(RT-qPCR)检测所筛选的差异miRNA的表达水平。应用受试者工作特征曲线(ROC曲线)、简易智力状态检查量表(MMSE)和蒙特利尔认知评估基础量表(MoCA_B)评分评价hsa-let-7d-3p对AD的诊断价值。此外,建立Aβ25~35损伤SH-SY5Y的细胞模型,采用RT-qPCR检测hsa-let-7d-3p水平。通过转染使细胞表达hsa-let-7d-3p,使用四唑盐法验证其是否影响Aβ25~35对细胞活力的作用。结果AD组MMSE评分、MoCA_B评分低于健康对照组(P<0.01)。在GSE120584与GSE46579中均上调的miRNA为hsa-miR-5001-3p、hsa-let-7d-3p、hsa-miR-589-5p、hsa-miR-4435、hsa-miR-3605-3p,均下调的miRNA为hsa-miR-548h-5p、hsa-miR-29c-3p。AD组血浆hsa-miR-5001-3p、hsa-let-7d-3p、hsa-miR-589-5p水平明显高于健康对照组(1.43±0.37比1.00±0.32,1.60±0.35比1.00±0.30,1.34±0.38比1.00±0.26)(P<0.01),血浆hsa-miR-29c-3p水平明显低于健康对照组(0.58±0.35比1.00±0.29)(P<0.01),两组hsa-miR-4435、hsa-miR-3605-3p、hsa-miR-548h-5p比较差异无统计学意义(P>0.05)。在AD患者血浆中变化最为显著的上调miRNA为hsa-let-7d-3p,hsa-let-7d-3p的ROC曲线下面积为0.910;AD患者血浆hsa-let-7d-3p与MMSE评分呈负相关(r=-0.536,P<0.01),与MoCA_B评分呈负相关(r=-0.617,P<0.01)。与控制组相比,Aβ25~35处理可显著降低SH-SY5Y细胞的活力(P<0.01);与Aβ+mimics NC组相比,Aβ+mimics组SH-SY5Y细胞活力下降(P<0.01),与Aβ+inhibitor NC组相比,Aβ+inhibitor组SH-SY5Y细胞活力升高(P<0.01)。结论AD患者和AD细胞模型中的hsa-let-7d-3p表达均上调,hsa-let-7d-3p在AD中参与病理Objective To explore the value and function of hsa-let-7d-3p for diagnosis of Alzheimer′s disease(AD).Methods A total of 80 AD patients who visited Xuzhou No.1 People′s Hospital from Apr.2018 to Mar.2022 were included as an AD group,and 60 healthy individuals were recruited as a healthy control group during the same period.The plasma miRNA of AD patients with significant changes in GSE46579 and GSE120584 data sets were screened,and the up-regulated and down-regulated miRNA in the two data sets were collected to screen biomarkers.The expression level of differential miRNA was detected by real-time quantified reverse transcription-polymerase chain reaction(RT-qPCR).The diagnostic value of hsa-let-7d-3p in AD was evaluated by receiver operating characteristic curve(ROC curve),mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA_B)scores.In addition,the cell model of SH-SY5Y injured by Aβ25-35 was established,and the level of hsa-let-7d-3p was detected by RT-qPCR.Cells were made to experss hsa-let-7d-3p by transfection,and methyl thiazolyl tetrazolium method was used to verify whether it could affect the effect of Aβ25-35 on cell viability.Results The MMSE score and MoCA_B score in the AD group were lower than those in the healthy control group(P<0.01).The miRNA up-regulated in both GSE120584 and GSE46579 were hsa-miR-5001-3p,hsa-let-7d-3p,hsa-miR-589-5p,hsa-miR-4435 and hsa-miR-3605-3p,and the knockdown miRNA were hsa-miR-548h-5p and hsa-miR-29c-3p.Plasma levels of hsa-miR-5001-3p,hsa-let-7d-3p,and hsa-miR-589-5p were significantly higher in the AD group than in the healthy control group(1.43±0.37 vs 1.00±0.32,1.60±0.35 vs 1.00±0.30,1.34±0.38 vs 1.00±0.26)(P<0.01),the plasma level of hsa-miR-29c-3p was significantly lower than that in the healthy control group(0.58±0.35 vs 1.00±0.29)(P<0.01).There was no significant difference between the two groups in hsa-miR-4435,hsa-miR-3605-3p,and hsa-miR-548h-5p(P>0.05).The most significantly up-regulated miRNA in plasma of AD patients was hsa

关 键 词：阿尔茨海默病 hsa-let-7d-3p 生物标志物 

分 类 号：R749.16[医药卫生—神经病学与精神病学]