新生儿缺氧缺血性脑病脑脊液中HIF-1α、AQP4的表达水平及意义

The relationship between HIF-1alpha,AQP4 and neonatal hypoxic-ischemic encephalopathy

目的探讨缺氧诱导因子(HIF-1α)、水通道蛋白(AQP4)在缺氧缺血性脑病(HIE)患儿脑脊液中的表达水平及意义。方法将诊治的80例HIE新生儿作为研究对象,并选取我院同期行腰椎穿刺术排除颅内感染的44例新生儿作为对照组。采用酶联免疫吸附法(ELISA)检测所有研究对象脑脊液中HIF-1α、AQP4及神经元特异性烯醇化酶(NSE)、钙结合蛋白(S-100β)水平;对所有研究对象进行NBNA评分;采用受试者工作特征曲线(ROC)评价HIF-1α、AQP4、NSE、S-100β对HIE的诊断价值。结果与对照组相比,HIE轻度组、HIE中重度组患儿脑脊液HIF-1α明显升高(P<0.05),且随着病情加重明显升高,而HIE轻度组患儿脑脊液AQP4无明显升高(P>0.05),HIE中重度组患儿脑脊液AQP4明显高于HIE轻度组患儿(P<0.05)。与对照组相比,HIE轻度组、HIE中重度组患儿脑脊液NSE、S-100β明显升高(P<0.05),而NBNA评分明显降低(P<0.05);HIE患儿脑脊液HIF-1α、AQP4水平均与NBNA评分呈负相关(P<0.05),与NSE、S-100β水平呈正相关(P<0.05)。脑脊液NSE、S-100β水平对HIE诊断的曲线下面积(AUC)分别为0.774、0.809,脑脊液HIF-1α、AQP4水平对HIE诊断的曲线下面积(AUC)分别为0.824、0.696。结论随着HIE患儿严重程度的增加,脑脊液中HIF-1α、AQP4水平呈升高的趋势,且二者对HIE的诊断价值也较高,推测HIF-1α、AQP4参与HIE的发生与进展,可作为评估HIE发生发展的生物标志物。

Objective To investigate the expressionof hypoxia-inducible factor-1α(HIF-1α) and aquaporin-4(AQP4) in cerebrospinal fluid of neonates with hypoxic-ischemic encephalopathy(HIE). Methods 80 neonates diagnosed with HIE and treated in our hospital were selected as study group. 44 neonates with wet lung,hypopharyngeal syndrome and without hypoxia,infection and other symptoms were selected as control group. The levels of HIF-1α,AQP4,neuron-specific enolase(NSE) and calcium binding protein(S-100β) in cerebrospinal fluid of all subjects were detected by enzyme-linked immunosorbent assay(ELISA),NBNA scores were recorded. The diagnostic values of HIF-1α,AQP4,NSE and S-100β in HIE were evaluated by ROC.Results Comparing with the control group,HIF-1α in children’s cerebrospinal fluid inmoderate and severe HIE groups increased significantly(P<0.05),and increased significantly with the aggravation of the disease. However,the level of AQP4 in children’s cerebrospinal fluid in HIE did not increase significantly(P>0.05),the level of AQP4 in children’s cerebrospinal fluid in moderate and severe HIE was significantly higher than those in mild HIE(P<0.05). Compared with the control group,NSE and S-100β in children’s cerebrospinal fluid increased significantly in mild,moderate and severe HIE groups(P<0.05),while NBNA scores decreased significantly(P<0.05). The levels of HIF-1αand AQP4 in children’s cerebrospinal fluid were negatively which correlated with NBNA scores(P<0.05),and positively correlated with NSE and S-100 beta levels(P<0.05). The areas under curve of cerebrospinal fluid NSE and S-100β levels for HIE diagnosis were respectively 0.774 and 0.809,and the areas under curve of cerebrospinal fluid HIF-1α and AQP4 levels for HIE diagnosis were respectively 0.824 and 0.715.Conclusion With the increasing of severity in HIE,the levels of HIF-1α and AQP4 in cerebrospinal fluid shows an increasing trend,and the diagnostic value for HIE is higher. It may speculated that HIF-1αand AQP4 participate in occurrence and progress of HIE which can be used as biomarkers to evaluate the occurrence and development of HIE.