血清HIF-1α水平与急性缺血性脑卒中患者静脉溶栓后症状性脑出血发生及预后的关联性研究

A study on the association of serum HIF-1αlevel with symptomatic cerebral hemorrhage and prognosis after intravenous thrombolysis in patients with acute ischemic stroke

目的分析血清低氧诱导因子-1α(HIF-1α)水平与急性缺血性脑卒中(AIS)患者静脉溶栓后症状性脑出血(sICH)发生及预后的关联性。方法招募2019年1月至2021年2月中国中医科学院西苑医院收治的AIS患者229例,均在发病4.5 h内接受重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗,以治疗后36 h发生sICH的情况将其分为sICH组(25例)和非sICH组(204例)。使用改良Rankin量表(mRS)评分评估患者治疗后3个月的功能预后情况。采用夹心式酶联免疫吸附试验法测定血清HIF-1α水平。结果sICH组患者入院时美国国立卫生研究院脑卒中量表(NIHSS)评分、空腹血糖(FBG)和HIF-1α水平均高于非sICH组,且合并糖尿病和既往有脑卒中史的人数比例较非sICH组更高,差异有统计学意义(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,血清HIF-1α水平具有预测AIS患者发生sICH的应用价值[AUC(95%CI)=0.886(0.815~0.957),P<0.001],最佳截断值为1.96 ng/ml,其对应的灵敏度和特异度分别为88.0%、78.4%。Cox回归分析结果显示,溶栓前血清HIF-1α≥1.96 ng/ml是AIS患者发生sICH的危险因素(P<0.05)。Spearman秩相关分析结果显示,血清HIF-1α水平与患者治疗后的mRS评分呈正相关(r_(s)=0.137,P=0.038)。经校正年龄、性别、吸烟史、合并症史等混杂因素后,多元线性逐步回归分析结果显示,血清HIF-1α水平是影响AIS患者治疗后mRS评分的独立因素(t=2.069,β=0.324,P=0.026)。结论血清HIF-1α水平升高与AIS患者rt-PA静脉溶栓后继发sICH风险增加和短期预后不良有关。

Objective To analyse the association of serum hypoxic inducible factor-1α(HIF-1α)level with symptomatic cerebral hemorrhage(sICH)and prognosis after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods Two hundred and twenty-nine AIS patients admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2019 to February 2021 were recruited,all of whom received intravenous thrombolytic treatment with recombinant tissue plasminogen activator(rt-PA)within 4.5 hours of onset.According to the occurrence of sICH 36 hours after treatment,the patients were divided into sICH group(25 cases)and non-sICH group(204 cases).The modified Rankin Scale(mRS)score was used to assess the patients′functional outcomes 3 months after treatment.The serum HIF-1αlevel was determined by sandwich enzyme-linked immunosorbent assay.Results The National Institute of Health Stroke Scale(NIHSS)scores,fasting blood glucose(FBG)and HIF-1αlevel in the sICH group were higher than those in the non-sICH group at admission,and the proportion of the patients with diabetes mellitus and previous history of stroke in the sICH group was higher than that in the non-sICH group,with statistically significant differences between the two groups(P<0.05).The results of receiver operating characteristic(ROC)curve analysis showed that serum HIF-1αlevel had application value in predicting the occurrence of sICH in the AIS patients[AUC(95%CI)=0.886(0.815-0.957),P<0.001],and the optimal cut-off value was 1.96 ng/ml.The corresponding sensitivity and specificity were 88.0%and 78.4%,respectively.The results of Cox regression analysis showed that serum HIF-1α≥1.96 ng/ml before thrombolysis was a risk factor fors ICH in the AIS patients(P<0.05).The results of Spearman rank correlation analysis showed that serum HIF-1αlevel was positively correlated with mRS scores after treatment for the patients(r_(s)=0.137,P=0.038).After adjusting the confounding factors such as age,gender,smoking history and history of complications,the results of multiple linearstepwise regression analysis showed that serum HIF-1αlevel was an independent factor affecting the mRS scores of the AIS patients after treatment(t=2.069,β=0.324,P=0.026).Conclusion Elevated serum HIF-1αlevel is associated with an increased risk of secondary sICH and poor short-term prognosis after intravenous thrombolysis of rt-PA in AIS patients.