血清HIF-2α、miR-21表达与动脉瘤性蛛网膜下腔出血患者介入栓塞术后脑血管痉挛的关系  

Relations of expressions of serum hypoxia inducible factor 2αand miR-21 with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage after interventional embolization

作　　者：王栋 吴环立[1] 高飞[1] 李琳坤 酒晓盈 赵海洋[1] Wang Dong;Wu Huanli;Gao Fei;Li Linkun;Jiu Xiaoying;Zhao Haiyang(Department of Neurosurgery,Nanyang Second General Hospital,Nanyang 473012,China)

机构地区：[1]南阳市第二人民医院神经外科,473012

出　　处：《中华神经医学杂志》2021年第4期340-345,共6页Chinese Journal of Neuromedicine

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20191469);河南省医学科技攻关计划(2018020983);南阳市科技攻关计划(KJGG120、KJGG166、KJGG185)。

摘　　要：目的探讨血清缺氧诱导因子-2α(HIF-2α)、微小RNA(miR)-21表达与动脉瘤性蛛网膜下腔出血患者介入栓塞术后脑血管痉挛的关系。方法前瞻性选取南阳市第二人民医院神经外科自2017年10月至2019年6月行介入栓塞术治疗的174例动脉瘤性蛛网膜下腔出血患者为研究对象,术后4 d行DSA检查并评估脑血管痉挛的严重程度,并于介入栓塞术前及术后3 d、7 d采用酶联免疫吸附法测定患者血清HIF-2α水平,采用逆转录-PCR(RT-PCR)测定血清miR-21的表达水平。比较不同脑血管痉挛程度患者的临床资料及血清HIF-2α、miR-21水平的变化。采用相关性分析检测患者术后3 d、7 d血清HIF-2α与miR-21水平的相关性。采用受试者工作特征(ROC)曲线分析术后3 d患者血清HIF-2α、miR-21水平对脑血管痉挛的诊断价值。结果174例患者中无、轻度、中度、重度脑血管痉挛患者分别为100、20、38、16例。无、轻度、中度、重度脑血管痉挛患者术后3 d、7 d血清HIF-2α、miR-21的水平均依次增加,各组间差异均有统计学意义(P<0.05)。患者术后3 d、7 d血清HIF-2α与miR-21的水平均呈正相关关系(P<0.05)。术后3 d,患者血清HIF-2α诊断脑血管痉挛的曲线下面积(AUC)为0.748(95%CI:0.615~0.883,P=0.000),血清miR-21诊断脑血管痉挛的AUC为0.715(95%CI:0.590~0.842,P=0.000),血清HIF-2α联合miR-21诊断脑血管痉挛的AUC为0.893(95%CI:0.792~0.985,P=0.000)。取HIF-2α、miR-21的诊断临界点为82.75 pg/mL、1.15时,血清HIF-2α联合miR-21检测诊断脑血管痉挛的敏感度、准确度、阴性预测值均高于HIF-2α、miR-21单独检测。结论动脉瘤性蛛网膜下腔出血患者介入栓塞术后血清HIF-2α、miR-21的水平能够有效预测脑血管痉挛的发生,并可能参与脑血管痉挛的发生及发展。Objective To investigate the relations of serum hypoxia inducible factor 2α(HIF-2α)and miR-21 expressions with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage(aSAH)after interventional embolization.Methods One hundred and seventy-four patients with aSAH underwent interventional embolization in our hospital from October 2017 to June 2019 were prospectively selected.DSA examination was performed 4 d after surgery,and severity of cerebral vasospasm was evaluated.Enzyme-linked immunosorbent assay was used to detect the level of serum HIF-2αand reverse transcription-PCR was employed to detect the serum miR-21 expression before and 3 and 7 d after interventional embolization.The clinical data and changes of serum HIF-2αand miR-21 expressions in patients with different degrees of cerebral vasospasm were compared.Correlation analysis was performed to analyze the relation of HIF-2αexpression with miR-21 expression 3 and 7 d after interventional embolization.Receiver operating characteristics curve was used to analyze the diagnostic values of serum HIF-2αand miR-21 levels in cerebral vasospasm 3 d after interventional embolization.Results There were 100 patients without vasospasm,and 20,38 and 16 patients with mild,moderate and severe cerebral vasospasm,respectively.The serum levels of HIF-2αand miR-21 in patients with mild,moderate and severe cerebral vasospasm increased successively 3 and 7 d after interventional embolization,with significant differences(P<0.05).Positive correlation was noted between expressions of HIF-2αand miR-21 in serum 3 and 7 d after interventional embolization(P<0.05).Area under the curve(AUC)of HIF-2αin diagnosis of cerebral vasospasm was 0.748(95%CI:0.615-0.883,P=0.000)3 d after interventional embolization.AUC of serum miR-21 level in diagnosis of cerebral vasospasm was 0.715(95%CI:0.590-0.842,P=0.000).AUC of serum HIF-2αcombined with miR-21 in diagnosis of cerebral vasospasm was 0.893(95%CI:0.792-0.985,P=0.000).When diagnostic critical points of HIF-2αand miR-2

关 键 词：动脉瘤性蛛网膜下腔出血 介入栓塞术 脑血管痉挛 缺氧诱导因子2α 微小RNA-21 

分 类 号：R743.35[医药卫生—神经病学与精神病学]