痴呆患者血清miR-9、miR-34c表达变化及意义

Expression changes of serum microRNA-9 and microRNA-34c in patients with dementia and its clinical significance

目的观察痴呆患者血清微小RNA-9(miR-9)、miR-34c表达变化,并探讨其临床意义。方法选择痴呆患者135例,根据临床痴呆分级量表评分分为轻度痴呆组59例、中度痴呆组45例、重度痴呆组31例,同期选择健康体检非痴呆患者60例作为对照组。采集痴呆患者入院次日及对照组体检时清晨空腹肘静脉血并分离血清,用罗氏P800全自动生化分析仪检测血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),用双抗体夹心法检测血清脂联素(ADP),用酶联免疫吸附法检测血清同型半胱氨酸(Hcy),用简易精神状态检查量表(MMSE)评分评价认知功能,用实时荧光定量PCR法(RT-qPCR)检测血清miR-9、miR-34表达。用Pearson积矩相关法分析各指标的相关性,用受试者工作特征(ROC)曲线评估血清miR-9、miR-34c对痴呆的诊断价值。结果各组HDL-C、LDL-C、ADP、Hcy、MMSE评分比较差异有统计学意义(P均<0.05)。与对照组比较,轻、中、重度痴呆组血清miR-9表达低(P均<0.05),血清miR-34c表达高(P均<0.05);痴呆病情越重,血清miR-9表达越低,血清miR-34c表达越高。痴呆患者血清miR-9与HDL-C、ADP、MMSE评分呈正相关(P均<0.05),与LDL-C、Hcy呈负相关(P均<0.05);血清miR-34c与HDL-C、ADP、MMSE评分呈负相关(P均<0.05),与LDL-C、Hcy呈正相关(P均<0.05)。血清miR-9、miR-34c诊断痴呆的ROC曲线下面积(AUC)分别为0.811、0.838,截断值分别为0.82、1.01;二者联合检测诊断痴呆的AUC为0.923。结论痴呆患者血清miR-9低表达、miR-34c高表达,二者表达变化可反映患者病情严重程度,二者联合检测可辅助诊断痴呆。

Objective To explore the expression changes of serum microRNA-9 (miR-9) and miR-34c in patients with dementia and its clinical significance.Methods A total of 135 senile patients with dementia were divided into the mild group ( n =59),moderate group ( n =45) and severe group ( n =31) according to the Clinical Dementia Scale (CDR).Meanwhile,60 non-dementia patients in the same period of health examination were selected as the control group.Fasting elbow venous blood was collected and the serum was separated from patients with dementia on the next day of admission and from patients in the control group in the morning during physical examination.Serum total cholesterol (TC),triglyceride (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C) were detected by Roche P800 automatic biochemical analyzer,the serum ADP was detected by double antibody sandwich method,serum Hcy was detected by enzyme-linked immunosorbent assay,and cognitive function was evaluated by MMSE score.The serum miR-9 and miR-34c were detected by real-time fluorescence quantitative PCR (RT-qPCR),the correlation of various indicators was analyzed by Person product moment correlation,and the diagnostic value of miR-9 and miR-34c on senile dementia was evaluated by receiver operating characteristic curve (ROC). Results The HDL-C,LDL-C,ADP,Hcy and scores of MMSE in each group were significantly different (all P <0.05).Compared with the control group,the mild,moderate and severe dementia group had lower expression of serum miR-9 and higher expression of serum miR-34c.The more severe dementia,the lower expression of serum miR-9 and the higher expression of serum miR-34c.Serum miR-9 was positively correlated with HDL-C,ADP and MMSE scores ( P <0.05),and was negatively correlated with LDL-C and Hcy (both P <0.05);serum miR-34c was negatively correlated with HDL-C,ADP and MMSE scores (all P <0.05),and was positively correlated with LDL-C and Hcy (both P <0.05).The area under the ROC curve (AUC) of serum miR-9 and miR-34c in diagnosis of dementia was 0.811,and the cut-off values was 0.82 and 1.01,respectively.The AUC of the combined detection of miR-9 and miR-34c in the diagnosis of dementia was 0.923. Conclusion The expression of serum miR-9 is low and miR-34c is high in dementia patients,the changes of the expression of miR-9 and miR-34c could reflect the severity of dementia,and the combined detection of miR-9 and miR-34c could be used as markers for assistant diagnosis of dementia.