MMP-9/TIMP-1平衡在急性缺血性脑卒中rt-PA溶栓后出血性转化中的临床应用研究

The clinical application of MMP-9/TIMP-1 balance in hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke

目的评估血清MMP-9/TIMP-1平衡对急性缺血性脑卒中rt-PA溶栓后出血性转化(hemorrhagic transformation,HT)的早期预测价值。方法选择2021年5月~2022年8月就诊于我院的急性缺血性脑卒中并接受rt-PA溶栓患者60例为研究对象。根据影像学证据将其分为HT组和非HT组,各30例,选择同期健康体检者30例作为对照组。临床治疗前及rt-PA溶栓后24h收集患者血液标本,酶联免疫吸附试验分别检测3组血清MMP-9及TIMP-1表达水平。利用受试者工作曲线评价血清MMP-9/TIMP-1在急性缺血性脑卒中rt-PA溶栓后HT中的早期预测价值。同时分析血清MMP-9/TIMP-1在急性缺血性脑卒中rt-PA溶栓前后的水平差异。结果在溶栓治疗前,HT组血清MMP-9的表达水平[31.63(15.97)ng/ml]高于非HT组[15.42(13.62)ng/ml](P<0.01)及对照组[16.57(6.41)ng/ml](P<0.01),HT组血清TIMP-1表达水平[3.82(2.53)ng/ml]与非HT组[3.11(2.42)ng/ml]比较,差异无统计学意义(P>0.05),但低于对照组[6.73(3.30)ng/ml](P<0.01)。在rt-PA溶栓治疗后24h,HT组血清MMP-9/TIMP-1水平[7.01(0.93)]高于非HT组[2.30(5.55)],差异具有统计学意义(P<0.01)。ROC曲线分析显示,血清MMP-9/TIMP-1预测急性缺血性脑卒中rt-PA溶栓后HT的曲线下面积为0.756。溶栓后血清MMP-9/TIMP-1水平明显下降[6.78(5.75)<8.61(6.90)](P<0.01)。结论临床治疗前血清MMP-9/TIMP-1平衡在急性缺血性脑卒中rt-PA溶栓后HT的患者中显著升高,其有望成为急性缺血性脑卒中rt-PA溶栓后HT的早期预测指标。

Objective To evaluate the value of serum MMP-9/TIMP-1 balance in early prediction of hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke.Methods A total of 60 patients with acute ischemic stroke who received rt-PA thrombolysis in our hospital from May 2021 to Aug 2022 were enrolled in this retrospective study.According to the imaging evidence,they were divided into hemorrhagic transformation group(30 cases)and non-hemorrhagic transformation group(30 cases),and 30 healthy people were collected as control group.Blood samples were collected before clinical treatment and 24 hours after rt-PA thrombolysis.The expression levels of serum MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay.The receiver operating characteristic curve was used to evaluate the early predictive value of serum MMP-9/TIMP-1 in hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke.At the same time,the expression difference of MMP-9/TIMP-1 in serum before and after rt-PA thrombolysis in acute ischemic stroke was analyzed.Results Before thrombolytic therapy,the expression level of serum MMP-9 in HT group[31.63(15.97)ng/ml]was higher than that in non-HT group[15.42(13.62)ng/ml](P<0.01)and control group[16.57(6.41)ng/ml](P<0.01).The expression level of serum TIMP-1 in HT group[3.82(2.53)ng/ml]was not significantly different from that in non-HT group[3.11(2.42)ng/ml](P>0.05),but it was lower than that in control group[6.73(3.30)ng/ml](P<0.01).After rt-PA thrombolysis treatment,serum MMP-9/TIMP-1 of HT group[7.01(0.93)]was higher than that of non-HT group[2.30(5.55)](P<0.01).ROC curve analysis showed that the area under the curve of serum MMP-9/TIMP-1 for predicting hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke was 0.756.The expression of MMP-9/TIMP-1 in serum decreased significantly after thrombolysis[6.78(5.75)<8.61(6.90)](P<0.01).Conclusion Before clinical treatment,serum MMP-9/TIMP-1 balance is significantly increased in patients with hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke.It may be an early predictor of hemorrhagic transformation after rt-PA thrombolysis in acute ischemic stroke.