缺氧诱导因子1α、Bcl-2/腺病毒E1B19kDa相互作用蛋白3在儿童创伤性脑损伤中的表达及意义

Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury

摘要:

目的 动态观察缺氧诱导因子1α（hypoxia-inducible factor 1α, HIF-1α）、Bcl-2/腺病毒E1B19kDa相互作用蛋白3（Bcl-2/adenovirus E1B19kDa-interacting protein 3, BNIP3）在儿童创伤性脑损伤（traumatic brain injury, TBI）中的变化，并评估其预测儿童TBI病情轻重及预后的临床价值。方法 前瞻性纳入2021年1月—2023年7月47例中重度TBI患儿为研究对象，根据格拉斯哥昏迷评分分为中度亚组（9~12分）和重度亚组（3~8分）；以同期因腹股沟斜疝诊治且无基础疾病的30例患儿为对照组。比较各组HIF-1α、BNIP3、自噬相关蛋白Beclin-1及S100B水平的差异，采用受试者操作特征曲线（receiver operating characteristic curve, ROC曲线）评估HIF-1α、BNIP3、Beclin-1及S100B对TBI病情轻重及预后的预测价值。结果 TBI组患儿血清HIF-1α、BNIP3、Beclin-1、S100B水平高于对照组（P<0.05）；TBI患儿中，重度亚组HIF-1α、BNIP3、Beclin-1、S100B水平高于中度亚组（P<0.05）。相关性分析显示，血清HIF-1α、BNIP3、Beclin-1、S100B水平与格拉斯哥昏迷评分呈负相关（P<0.05）。治疗7 d后，非手术TBI和手术TBI患儿的血清HIF-1α、BNIP3、Beclin-1及S100B水平均较治疗前下降（P<0.05）。ROC曲线分析显示，血清HIF-1α、BNIP3、Beclin-1、S100B水平预测重度TBI的曲线下面积分别为0.782、0.835、0.872、0.880（P<0.05），预测TBI预后不良的曲线下面积分别为0.749、0.775、0.814、0.751（P<0.05）。结论 TBI患儿血清HIF-1α、BNIP3及Beclin-1水平显著升高，检测其水平有助于临床判断TBI患儿的病情轻重及预后。

Abstract:

Objective To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI.Methods A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves.Results Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05).Conclusions Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.