动脉瘤性蛛网膜下腔出血患者开颅夹闭术后血清KLF5 mRNA和lncRNA NEAT1表达及其与认知功能的相关性研究

Correlation between serum KLF5 mRNA and lncRNA NEAT1 expression and cognitive function in patients with aneurysmal subarachnoid hemorrhage after craniotomy clipping

目的探讨动脉瘤性蛛网膜下腔出血患者开颅夹闭术后血清Kruppel样因子5(KLF5)微小RNA(mRNA)和长链非编码RNA核富含丰富的转录本1(lncRNA NEAT1)表达与认知功能的相关性。方法选取2021年2月至2022年4月在该院进行开颅夹闭术的110例动脉瘤性蛛网膜下腔出血患者作为研究对象。术后根据认知功能的评分分为认知功能正常(≥26分,对照组)和认知功能障碍(<26分,研究组)。采用实时荧光定量聚合酶链反应检测血清KLF5 mRNA和lncRNA NEAT1水平;采用简易精神状态量表(MMSE)和蒙特利尔认知评估量表(MoCA)评分评定患者的认知功能水平;采用Pearson相关分析血清KLF5 mRNA与lncRNA NEAT1的相关性及二者与认知功能障碍的相关性;采用多因素Logistic回归分析动脉瘤性蛛网膜下腔出血患者认知功能障碍的影响因素;绘制受试者工作特征(ROC)曲线分析血清KLF5 mRNA和lncRNA NEAT1水平单独及二者联合对动脉瘤性蛛网膜下腔出血患者认知功能障碍的诊断价值。结果对照组纳入67例患者,研究组纳入43例患者。术后早期研究组血清KLF5 mRNA和lncRNA NEAT1水平均显著高于对照组,且术后早期血清KLF5 mRNA和lncRNA NEAT1水平均显著高于术前,差异均有统计学意义(P<0.05)。研究组MMSE和MoCA评分均显著低于对照组,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,血清KLF5 mRNA和lncRNA NEAT1水平呈正相关(P<0.05),且二者均与MMSE和MoCA评分均呈负相关(P<0.05)。多因素Logistic回归分析结果显示,KLF5 mRNA、lncRNA NEAT1高表达均为动脉瘤性蛛网膜下腔出血患者认知功能障碍的危险因素(P<0.05)。ROC曲线分析结果显示,KLF5 mRNA诊断动脉瘤性蛛网膜下腔出血患者认知功能障碍的曲线下面积(AUC)为0.814,lncRNA NEAT1诊断动脉瘤性蛛网膜下腔出血患者认知功能障碍的AUC为0.872,二者联合诊断动脉瘤性蛛网膜下腔出血患者认知功能障碍的AUC为0.950,二者联合诊断优于KLF5和lncRNA NEAT1各自单独诊断(Z联合vs.KLF5mRNA=2.547、Z联合vs.lncRNA NEAT1=3.268,P<0.05)。结论动脉瘤性蛛网膜下腔出血患者开颅夹闭术后血清KLF5 mRNA和lncRNA NEAT1表达升高与认知功能障碍有关,二者联合检测可以更好地预测认知功能障碍的发生。

Objective To investigate the correlation between the expression of serum Kruppel-like factor 5(KLF5)microRNA(mRNA)and long non-coding RNA nuclear rich and abundant transcript 1(lncRNA NEAT1)and cognitive function in patients with aneurysmal subarachnoid hemorrhage after craniotomy clipping.Methods A total of 110 patients with aneurysmal subarachnoid hemorrhage who underwent craniotomy clipping in this hospital from February 2021 to April 2022 were selected as the research objects.According to the postoperative cognitive function score,the patients were divided into normal cognitive function(≥26 points,control group)and cognitive dysfunction(<26 points,study group).The levels of KLF5 mRNA and lncRNA NEAT1 in serum were detected by real-time fluorescence quantitative polymerase chain reaction.Cognitive function was assessed by Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Pearson correlation was used to analyze the correlation between serum KLF5 mRNA and lncRNA NEAT1 and their correlation with cognitive dysfunction.Multivariate Logistic regression was used to analyze the influencing factors of cognitive dysfunction in patients with aneurysmal subar achnoid hemorrhage.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum KLF5 mRNA and lncRNA NEAT1 levels alone or in combination for cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage.Results There were 67 patients in the control group and 43 patients in the study group.The levels of serum KLF5 mRNA and lncRNA NEAT1 in the study group were significantly higher than those in the control group in the early postoperative period,and the levels of serum KLF5 mRNA and lncRNA NEAT1 in the early postoperative period were significantly higher than those before operation,and the differences were statistically significant(P<0.05).The MMSE and MoCA scores of the study group were significantly lower than those of the control group,and the differences were statistically significant(P<0.05).Pearson correlation analysis showed that serum KLF5 mRNA and lncRNA NEAT1 levels were positively correlated(P<0.05),and both were negatively correlated with MMSE and MoCA scores(P<0.05).Multivariate Logistic regression analysis showed that the high expressions of KLF5 mRNA and lncRNA NEAT1 were risk factors for cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of KLF5 mRNA in the diagnosis of cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage was 0.814,and the AUC of lncRNA NEAT1 in the diagnosis of cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage was 0.872,the AUC of the combination of the two in the diagnosis of cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage was 0.950,and the combination diagnosis of the two was better than KLF5 mRNA and lncRNA NEAT1 alone(Z combined vs.KLF5 mRNA=2.547,Z combined vs.lncRNA NEAT1=3.268,P<0.05).Conclusion The increased expression of serum KLF5 and lncRNA NEAT1 after craniotomy in patients with aneurysmal subarachnoid hemorrhage is related to cognitive dysfunction,and the combined detection of the two can better predict the occurrence of cognitive dysfunction.