Abstract
Objective:Acute cerebral infarction(ACI)is frequently accompanied by neuronal injury throughout its onset and progression.Vascular endothelial zinc finger protein 1(VEZF1),glial fibrillary acidic protein(GFAP),and nuclear factor kappa B(NF-κB)are involved in mediating neuronal injury and may interact with one another.This study aims to investigate the predictive value of serum VEZF1,GFAP and NF-κB levels for clinical deterioration after intravenous thrombolytic therapy with recombinant tissue plasminogen activator(rt-PA)alteplase in patients with ACI,thereby providing evidence for the diagnosis and management of ACI.
Methods:Patients with ACI who underwent intravenous rt-PA(alteplase)thrombolysis between January 2020 and September 2025 were retrospectively enrolled.Baseline clinical data were collected.Serum levels of VEZF1,GFAP,and NF-κB were measured by enzyme-linked immunosorbent assay(ELISA)at admission(T0),6 hours after thrombolysis(T1),and 24 hours after thrombolysis(T2).The therapeutic effect of thrombolysis was evaluated using the National Institutes of Health Stroke Scale(NIHSS).According to whether clinical deterioration occurred after thrombolysis,patients were divided into a deterioration group and a non-deterioration group.Baseline clinical characteristics and serum levels of VEZF1,GFAP,and NF-κB were compared between the 2 groups.Multivariate Logistic regression analysis was performed to identify factors associated with clinical deterioration after intravenous rt-PA thrombolysis in patients with ACI.Pearson correlation analysis was used to assess the relationships among VEZF1,GFAP,and NF-κB.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive performance of serum VEZF1,GFAP,and NF-κB levels for post-thrombolytic deterioration.
Results:A total of 170 patients with ACI who received intravenous rt-PA thrombolysis were included.Among them,41 patients experienced deterioration after thrombolysis,whereas 129 did not.Compared with the non-deterioration group,the deterioration group had a longer onset-to-thrombolysis time,higher NIHSS scores at admission,and a higher proportion of hemorrhagic transformation(all P<0.05).Repeated-measures analysis of variance showed significant temporal changes in serum VEZF1,GFAP,and NF-κB levels in both groups(time effect:P<0.05),significant differences between groups(group effect:P<0.05),and significant time-by-group interactions(P<0.05).At all time points from T0 to T2,serum GFAP and NF-κB levels were significantly higher in the deterioration group than in the non-deterioration group,whereas serum VEZF1 levels were significantly lower(Bonferroni-corrected,all P<0.017).Multivariate Logistic regression analysis demonstrated that onset-to-thrombolysis time(OR=1.425),NIHSS score at admission(OR=1.589),serum GFAP level(OR=1.730),and serum NF-κB level(OR=1.677)were independent risk factors for clinical deterioration after intravenous rt-PA thrombolysis,whereas serum VEZF1 level(OR=0.609)was an independent protective factor(all P<0.05).Pearson correlation analysis showed that at T0,GFAP was positively correlated with NF-κB(r=0.682,P<0.001),whereas VEZF1 was negatively correlated with both GFAP and NF-κB(r=-0.594 and-0.615,respectively,both P<0.001).ROC curve analysis demonstrated that the combination of serum VEZF1,GFAP,and NF-κB achieved an area under the curve(AUC)of 0.827 for predicting post-thrombolysis deterioration,with a sensitivity of 84.75％and a specificity of 82.31％,outperforming each biomarker alone.External validation of the prediction model showed an AUC of 0.804,with a sensitivity of 83.14％and a specificity of 80.75％for predicting deterioration after rt-PA thrombolysis.Bootstrap validation with 1 000 resamples yielded a concordance index(C-index)of 0.800(95％CI 0.732 to 0.895).Calibration curve analysis demonstrated good agreement between predicted and observed outcomes.
Conclusion:Patients with ACI who experience clinical deterioration after intravenous thrombolysis with rt-PA exhibit elevated serum GFAP and NF-κB levels and reduced serum VEZF1 levels.The combined assessment of these three biomarkers provides good predictive value for identifying the risk of deterioration after thrombolysis therapy.关键词
急性脑梗死/重组组织型纤溶酶原激活物/阿替普酶/静脉溶栓/恶化/血管内皮锌指蛋白1/胶质纤维酸性蛋白/核因子κBKey words
acute cerebral infarction/recombinant tissue plasminogen activator/alteplase/intravenous thrombolysis/deterioration/vascular endothelial zinc finger protein 1/glial fibrillary acidic protein/nuclear factor κB分类
医药卫生
