外周血单个核细胞锌指样转录因子2、锌指样转录因子4mRNA表达与脑梗死静脉溶栓预后的相关性分析

Correlation between the expression of KLF2 and KLF4 mRNA in peripheral blood mononuclear cells and the prognosis of cerebral infarction after intravenous thrombolysis

目的检测急性动脉粥样硬化性脑梗死(ACI)病人外周血单个核细胞锌指样转录因子家族(KLF)2、KLF4表达变化,并分析其与病人重组人组织型纤溶酶原激活剂(rt-PA)静脉溶栓后预后的关系。方法选取2016年4月至2018年4月郑州大学附属郑州中心医院就诊并接受rt-PA静脉溶栓治疗的ACI病人117例作为研究对象,并根据溶栓治疗结局将病人分为预后良好组和预后不良组。统计病人一般资料及24 h美国国立卫生研究院卒中量表(NIHSS)评分。利用实时定量PCR(qRT-PCR)法检测病人入院后及溶栓治疗24 h外周血单个核细胞KLF2、KLF4信使核糖核酸(mRNA)表达,酶联免疫吸附法(ELISA)法测定外周血白细胞介素(IL)-2、IL-6表达水平。结果与入院时比较,溶栓后24 h预后良好组病人外周血单个核细胞KLF2、KLF4 mRNA水平分别为(0.53±0.10)、(0.62±0.14)升高,外周血IL-2、IL-6表达水平分别为(4.08±0.85)、(4.19±0.74)降低(P<0.05),而预后不良组差异无统计学意义(P>0.05);与预后良好组比较,预后不良组病人入院时及溶栓后24 h外周血单个核细胞KLF2、KLF4 mRNA分别为(0.24±0.05)、(0.31±0.07)呈低表达,外周血IL-2、IL-6分别为(9.47±2.35)、(7.63±1.82)呈高表达(P<0.05);病人入院时外周血单个核细胞KLF2、KLF4 mRNA水平与90 d MRS评分负相关(r=-0.347、-0.349,均P<0.05);KLF2、KLF4 mRNA联合检测预测病人不良结局的AUC为0.970,灵敏度为85.90%,特异度为98.00%;logistic回归分析表明,入院时KLF2 mRNA≤0.36、KLF4 mRNA≤0.44、IL-2高表达、IL-6高表达、NIHSS评分>5分、糖尿病是溶栓治疗后ACI病人出现不良预后的危险因素(P<0.05)。结论预后不良病人入院时及溶栓后24 h外周血单个核细胞KLF2、KLF4 mRNA呈低表达,两者对急性动脉粥样硬化性脑梗死病人溶栓治疗90 d后结局具有一定预测价值。

Objective mononuclear cell of patients with acute atherosclerotic cerebral infarction(ACI),and to analyze their relationships with the prognosis of patients after recombinant human tissue type plasminogen activator(rt-PA)intravenous thrombolysis.Methods A total of 117 patients with ACI who received rt-PA intravenous thrombolytic therapy in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April 2016 to April 2018 were selected as the research objects,and they were divided into good prognosis group and poor prognosis group according to the outcome of thrombolytic therapy.The general information and 24 h National Institutes of Health Stroke Scale(NIHSS)score of the patients were analyzed.Real time quantitative PCR(qRT-PCR)was used to detect the expression of KLF2 and KLF4 mRNA in peripheral blood mononuclear cells after admission and 24 h after thrombolytic therapy.The expression levels of IL-2 and IL-6 in PBMC were determined by enzyme-linked immunosorbent assay(ELISA).Results Compared with those at the time of admission,the mRNA levels of KLF2 and KLF4 in peripheral blood mononuclear cells of patients with good prognosis 24 h after thrombolysis were(0.53±0.10),(0.62±0.14),the expression levels of IL-2 and IL-6 in peripheral blood were(4.08±0.85),(4.19±0.74)(P<0.05),there was no significant difference in poor prognosis group(P>0.05);Compared with the patients with good prognosis,the mRNA of KLF2 and KLF4 in the patients with poor prognosis at admission and 24 hours after thrombolysis were(0.24±0.05),(0.31±0.07),the levels of IL-2 and IL-6 in peripheral blood were(9.47±2.35)and(7.63±1.82)respectively(P<0.05);At admission,the levels of KLF2 and KLF4 in peripheral blood mononuclear cell were negatively correlated with 90 d MRS score(r=-0.347,-0.349,all P<0.05).The AUC of KLF2 and KLF4 mRNA combined detection was 0.970,the sensitivity was 85.90%,and the specificity was 98.00%.logistic regression analysis showed that KLF2 mRNA≤0.36,KLF4 mRNA≤0.44,IL-2 higher expression,IL-6 higher expression,NIHSS score>5 and diabetes mellitus were risk factors for adverse prognosis of ACI patients after thrombolytic therapy(P<0.05).Conclusion The expression of KLF2 and KLF4 mRNA in peripheral blood mononuclear cells of patients with poor prognosis at admission and 24 h after thrombolysis is low,and both of them have certain predictive value for 90 d outcome of patients with acute atherosclerotic cerebral infarction after thrombolytic therapy.