miRNAs及血清神经元PAS结构域蛋白4、神经元特异性烯醇化酶、S100β蛋白水平与急性脑卒中患者认知障碍严重程度的关系研究

Relations of miRNAs,Serum Levels of NPAS4,NSE and S100β Protein with Severity of Cognitive Disorder in Patients with Acute Stroke

背景认知障碍可影响急性脑卒中患者主动参与社会活动、配合肢体功能训练及生活质量,因此寻找有效评估急性脑卒中患者认知障碍严重程度的指标具有重要意义。目的探讨miRNAs及血清神经元PAS结构域蛋白4(NPAS4)、神经元特异性烯醇化酶(NSE)、S100β蛋白水平与急性脑卒中患者认知障碍严重程度的关系。方法选取2014年8月—2018年5月解放军三零七医院神经内科收治的急性脑卒中并认知障碍患者146例,根据认知障碍严重程度分为轻度组(n=101)、中度组(n=30)、重度组(n=15)。比较3组患者miRNAs(包括miRNA-34、miRNA-21、miRNA-135)相对表达量及血清NPAS4、NSE、S100β蛋白水平;miRNAs相对表达量及血清NPAS4、NSE、S100β蛋白水平与急性脑卒中患者认知障碍严重程度的相关性采用Spearman秩相关分析;绘制ROC曲线以评价miRNAs相对表达量及血清NPAS4、NSE、S100β蛋白水平对急性脑卒中患者认知障碍严重程度的评估价值。结果 (1)重度组患者miRNA-34、miRNA-21、miRNA-135相对表达量及血清NSE、S100β蛋白水平低于轻度组和中度组,血清NPAS4水平高于轻度组和中度组(P<0.05);中度组患者miRNA-34、miRNA-21、miRNA-135相对表达量及血清NSE、S100β蛋白水平低于轻度组,血清NPAS4水平高于轻度组(P<0.05)。(2)Spearman秩相关分析结果显示,miRNA-135相对表达量及血清NSE、S100β蛋白水平与急性脑卒中患者简明精神状态量表(MMSE)评分呈正相关(rs值分别为0.420、0.434、0.456,P<0.05),血清NPAS4水平与急性脑卒中患者MMSE评分呈负相关(rs=-0.448,P<0.01)。(3)ROC曲线分析结果显示,miRNA-135相对表达量评估急性脑卒中患者认知障碍严重程度的曲线下面积(AUC)为0.747,最佳截断值为0.71;血清NPAS4水平评估急性脑卒中患者认知障碍严重程度的AUC为0.729,最佳截断值为2.01 mg/L;血清NSE水平评估急性脑卒中患者认知障碍严重程度的AUC为0.751,最佳截断值为13.00 U/ml;血清S100β蛋白水平评估急性脑卒中患者认知障碍严重程度的AUC为0.755,最佳截断值为0.19μg/L。结论 miRNA-34、miRNA-21与急性脑卒中患者认知障碍严重程度无关,而miRNA-135及血清NPAS4、NSE、S100β蛋白水平与急性脑卒中患者认知障碍严重程度有关,且四者对急性脑卒中患者认知障碍严重程度具有一定评估价值。

Background Cognitive disorder may affect the active participation of social activity,cooperation of limb function training and quality of life in patients with acute stroke,therefore research about effective estimated index for severity of cognitive disorder in patients with acute stroke is of great importance.Objective To investigate the relations of miRNAs,serum levels of NPAS4,NSE and S100βprotein with severity of cognitive disorder in patients with acute stroke.Methods From August 2014 to May 2018,a total of 146 acute stroke patients complicated with cognitive disorder were selected in the Department of Neurology,the 307th Hospital of the Chinese People's Liberation Army,and they were divided into mild group(n=101),moderate group(n=30)and severe group(n=15)according to the severity of cognitive disorder.Relative expression quantity of miRNAs(including miRNA-34,miRNA-21 and miRNA-135),serum levels of NPAS4,NSE and S100βprotein were compared between the two groups;Spearman rank correlation analysis was used to analyze the correlations of relative expression quantity of miRNAs,serum levels of NPAS4,NSE and S100βprotein with severity of cognitive disorder in patients with acute stroke;ROC curve was drawn to evaluate the estimated value of relative expression quantity of miRNAs,serum levels of NPAS4,NSE and S100βprotein on severity of cognitive disorder in patients with acute stroke.Results(1)Relative expression quantity of miRNA-34,miRNA-21 and miRNA-135,serum levels of NSE and S100βprotein in severe group were statistically significantly lower than those in mild group and moderate group,while serum NPAS4 level in severe group was statistically significantly higher than that in mild group and moderate group,respectively(P<0.05);relative expression quantity of miRNA-34,miRNA-21 and miRNA-135,serum levels of NSE and S100βprotein in moderate group were statistically significantly lower than those in mild group,while serum NPAS4 level in moderate group was statistically significantly higher than that in mild group(P<0.05).(2)Spearman rank correlation analysis results showed that,relative expression quantity of miRNA-135(rs=0.420)and serum levels of NSE(rs=0.434)and S100βprotein(rs=0.465)was positively correlated with MMSE score in patients with acute stroke,respectively(P<0.05),while serum NPAS4 level(rs=-0.448)was negatively correlated with MMSE score in patients with acute stroke,respectively(P<0.01).(3)ROC curve showed that,AUC of relative expression quantity of miRNA-135 in estimating the severity of cognitive disorder in patients with acute stroke was 0.747,the optimum cut-off value was 0.71;AUC of serum NPAS4 level in estimating the severity of cognitive disorder in patients with acute stroke was 0.729,the optimum cut-off value was 2.01 mg/L;AUC of serum NSE level in estimating the severity of cognitive disorder in patients with acute stroke was 0.751,the optimum cut-off value was 13.00 U/ml;AUC of serum S100βprotein level in estimating the severity of cognitive disorder in patients with acute stroke was 0.755,the optimum cut-off value was 0.19μg/L.Conclusion In patients with acute stroke,miRNA-34 and miRNA-21 are not significantly correlated with the severity of cognitive disorder,while miRNA-135,serum levels of NPAS4,NSE and S100βprotein are significantly correlated with the severity of cognitive disorder,more the above four have certain estimated value on the severity of cognitive disorder.