血清miR-149-5p和基质金属蛋白酶-9预测急性缺血性卒中患者静脉溶栓后出血性转化

Serum miR-149-5p and matrix metalloproteinase-9 predict hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke

目的探讨血清miR-149-5p和金属基质蛋白酶(matrix metalloproteinase,MMP)-9与急性缺血性卒中(acute ischemic stroke,AIS)患者静脉溶栓后出血性转化(hemorrhagic transformation,HT)的相关性及其预测价值。方法前瞻性纳入2019年9月至2022年2月在商丘市第一人民医院接受静脉溶栓治疗的AIS患者,根据静脉溶栓后是否发生HT分为HT组与非HT组。应用实时荧光定量聚合酶链反应测定血清miR-149-5p,酶联免疫吸附法测定血清MMP-9。应用多变量logistic回归分析确定溶栓后HT的独立危险因素。应用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清miR-149-5p、MMP-9以及二者联合对静脉溶栓后HT的预测价值。结果共纳入358例接受静脉溶栓治疗的AIS患者,其中71例(19.83%)发生HT。HT组患者血清MMP-9显著高于非HT组[(273.95±35.23)μg/L对(202.71±30.52)μg/L;t=17.062,P<0.001],而血清miR-149-5p显著低于非HT组(0.26±0.06对1.03±0.15;t=42.387,P<0.001)。多变量logistic回归分析表明,心房颤动[优势比(odds ratio,OR)2.282,95%置信区间(confidence interval,CI)1.731~3.008;P<0.001]、发病至静脉溶栓时间(OR 2.334,95%CI 1.458~3.735;P<0.001)、miR-149-5p(OR 1.758,95%CI 1.142~2.705;P=0.010)和MMP-9(OR 1.535,95%CI1.106~2.129;P=0.010)是静脉溶栓后HT的独立危险因素。血清miR-149-5p(曲线下面积0.856,95%CI 0.803~0.909;最佳截断值为0.741时的敏感性为80.3%,特异性为89.9%)、MMP-9(曲线下面积0.875,95%CI 0.821~0.929;最佳截断值为240.051μg/L时的敏感性为83.1%,特异性为90.2%)以及两者联合(曲线下面积0.897,95%CI 0.854~0.941;敏感性为84.5%,特异性为90.6%)对溶栓后HT均具有较好的预测价值,而且三者之间的预测价值差异无统计学意义。结论AIS患者静脉溶栓后HT患者入院时血清miR-149-5p较低而MMP-9较高。二者及二者联合对静脉溶栓后HT均具有较好的预测价值。

Objective To investigate the correlation and predictive value of serum miR-149-5p and matrix metalloproteinase-9(MMP-9)and hemorrhagic transformation(HT)after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods Patients with AIS received intravenous thrombolytic therapy in Shangqiu First People's Hospital from September 2019 to February 2022 were enrolled prospectively.They were divided into HT group and non-HT group according to whether HT occurred after intravenous thrombolysis.Serum miR-149-5p and MMP-9 were measured by real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunosorbent assay respectively.Multivariate logistic regression analysis was used to determine the independent risk factors for HT after thrombolysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum miR-149-5p,MMP-9 and their combination for HT after intravenous thrombolysis.Results A total of 358 patients with AIS received intravenous thrombolytic therapy were enrolled,71 of them(19.83%)developed HT.The serum MMP-9 in the HT group was significantly higher than that in the non-HT group(273.95±35.23μg/L vs.202.71±30.52μg/L;t=17.062,P<0.001),while the serum miR-149-5p was significantly lower than that in the non-HT group(0.26±0.06 vs.1.03±0.15;t=42.387,P<0.001).Multivariate logistic regression analysis showed that atrial fibrillation(odds ratio[OR]2.282,95%confidence interval[CI]1.731-3.008;P<0.001),time from onset to intravenous thrombolysis(OR 2.334,95%CI 1.458-3.735;P<0.001),miR-149-5p(OR 1.758,95%CI 1.142-2.705;P=0.010)and MMP-9(OR 1.535,95%CI 1.106-2.129;P=0.010)were the independent risk factors for HT after intravenous thrombolysis.Serum miR-149-5p(area under the curve 0.856,95%CI 0.803-0.909;when the optimal cut-off value was 0.741,the sensitivity was 80.3%and the specificity was 89.9%),MMP-9(area under the curve 0.875,95%CI 0.821-0.929;when the optimal cut-off value was 240.051μg/L,the sensitivity was 83.1%and the specificity was 90.2%)and their combination(area under the curve 0.897,95%CI 0.854-0.941;sensitivity 84.5%and specificity 90.6%)had better predictive value for HT after thrombolysis,and there were no significant differences in the predictive value among the three.Conclusions After intravenous thrombolysis,the serum miR-149-5p is lower and MMP-9 is higher at admission in patients with HT in patients with AIS.Both of them and their combination have better predictive value for HT after intravenous thrombolysis.