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中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2022, Vol. 08 ›› Issue (06) : 346 -350. doi: 10.3877/cma.j.issn.2095-9141.2022.06.006

临床研究

早产儿脑损伤与血清中Tau、TLR4变化水平的关系研究
罗洁1,†(), 李杰1   
  1. 1. 617000　四川攀枝花，攀枝花市中西医结合医院儿科
  • 收稿日期:2022-09-06 出版日期:2022-12-15
  • 通信作者: 罗洁
  • 基金资助:
    四川省卫生和计划生育委员会科研课题(18PJ043)

Relationship between brain injury and changes of serum Tau and TLR4 levels in premature infants

Jie Luo1,†(), Jie Li1   

  1. 1. Department of Pediatrics, Panzhihua Integrated Traditional Chinese and Western Medicine Hospital, Panzhihua 617000, China
  • Received:2022-09-06 Published:2022-12-15
  • Corresponding author: Jie Luo
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引用本文：

罗洁, 李杰. 早产儿脑损伤与血清中Tau、TLR4变化水平的关系研究[J]. 中华神经创伤外科电子杂志, 2022, 08(06): 346-350.

Jie Luo, Jie Li. Relationship between brain injury and changes of serum Tau and TLR4 levels in premature infants[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2022, 08(06): 346-350.

目的

分析早产儿脑损伤（BIPI）血清中微管相关蛋白Tau和Toll样受体4（TLR4）表达水平及其与脑损伤严重程度的关系。

方法

收集攀枝花市中西医结合医院儿科自2018年10月至2020年5月出生的70例BIPI患儿作为脑损伤组，根据临床症状和头颅MRI检测结果，将其分为轻度脑白质损伤组（22例）、中度脑白质损伤组（27例）和重度脑白质损伤组（21例）。另选取同期出生的70例无脑损伤早产儿作为无脑损伤组。所有患儿均采用振幅整合脑电图（aEEG）监测BIPI脑功能。采用酶联免疫吸附测定（ELISA）法检测各组早产儿出生第1、3及7天血清Tau和TLR4蛋白表达水平。受试者工作特征（ROC）曲线分析血清Tau和TLR4水平对BIPI发生的预测价值。比较不同程度脑白质损伤早产儿血清Tau和TLR4的变化水平。

结果

无脑损伤组和脑损伤组患儿的性别比例、胎龄、出生体质量差异均无统计学意义（P>0.05）。脑损伤组患儿矫正胎龄足月时aEEG评分明显低于无脑损伤组，差异有统计学意义（P<0.05）。脑损伤组患儿出生后第1、3和7天的血清Tau和TLR4水平明显高于无脑损伤组，且随时间推移，血清Tau水平均逐渐下降，TLR4水平先升高后下降，差异均有统计学意义（P<0.05）。早产儿出生第1、3和7天联合检测血清Tau和TLR4水平对BIPI预测的AUC为0.639、0.930和0.887，其预测价值优于单项预测。各组患儿出生后第1、3及7天随着脑白质损伤程度的加重，血清Tau水平呈明显上升趋势，而血清TLR4水平在出生后3 d最高，差异均有统计学意义（P<0.05）。

结论

血清中Tau和TLR4表达与BIPI脑白质损伤程度有关，可作为评估BIPI病情发展程度。

关键词: 早产儿, 脑损伤, 微管相关蛋白Tau, Toll样受体4
Objective

To analyze the expression levels of microtubule-associated protein Tau and Toll-like receptor 4 (TLR4) in serum of preterm infants with brain injury (BIPI) and their relationship with the severity of brain injury.

Methods

A total of 70 BIPI born in Pediatrics Department of Panzhihua Integrated Traditional Chinese and Western Medicine Hospital from October 2018 to May 2020 were selected as the brain injury goup. According to clinical symptoms and examination results of head MRI, they were divided into mild brain white matter injury group (22 cases), moderate brain white matter injury group (27 cases) and severe brain white matter injury group (21 cases). Another 70 premature infants without brain injury born in the same period were selected as the non-brain injury group. The brain function of BIPI was monitored by amplitude integrated electroencephalogram (aEEG). On the 1st, 3rd and 7th day after birth, levels of serum microtubule-associated protein (Tau) and Toll-like receptor 4 (TLR4) in each group were detected by enzyme-linked immunosorbent assay (ELISA). The predictive value of serum Tau and TLR4 levels in different periods for BIPI was compared. The value of serum Tau and TLR4 levels in predicting the occurrence of BIPI was analyzed by receiver operating characteristic (ROC) curve. The changes in levels of serum Tau and TLR4 among premature infants with different degrees of brain white matter injury were compared.

Results

There was no significant difference in gender ratio, gestational age or birth weight between non-brain injury group and brain injury group (P>0.05). The aEEG score of full-term corrected gestational age in brain injury group was significantly lower than that in non-brain injury group (P < 0.05). On the 1st, 3rd and 7th day after birth, levels of serum Tau and TLR4 in brain injury group were significantly higher than those in non-brain injury group, and the level of serum Tau gradually decreased over time and the level of serum TLR4 increased first and then decreased. The AUC values predicted by BIPI by combined detection of serum Tau and TLR4 levels for preterm infants on the 1st, 3rd and 7th day after birth are 0.639, 0.930 and 0.887, which was better than the single prediction. On the 1st, 3rd and 7th day after birth, the level of serum Tau increased significantly with the severity of cerebral white matter injury and the level of serum TLR4 was the highest on the 3rd day after birth, the difference was statistically significant (P<0.05).

Conclusion

The expression of Tau and TLR4 in serum is related to the degree of cerebral white matter injury in children, which can be used to evaluate the progression of BIPI.

Key words: Premature infant, Brain injury, Microtubule associated protein Tau, Toll-like receptor-4
表1 2组早产儿的一般资料比较
组别 例数 性别（男/女） 胎龄（周，±s） 出生体质量（g，±s） 矫正胎龄足月时aEEG评分（分，±s）
无脑损伤组 70 40/30 31.71±0.82 1685.23±256.21 10.13±1.05
脑损伤组 70 42/28 31.62±0.71 1762.21±234.42 7.89±0.81
t/χ2值   0.118 0.694 1.854 14.132
P值   0.731 0.489 0.066 <0.001
表2 2组早产儿不同时期血清Tau和TLR4水平比较（ng/mL，±s）
组别 例数 Tau TLR4
第1天 第3天 第7天 F值 P值 第1天 第3天 第7天 F值 P值
无脑损伤组 70 0.56±0.05 0.36±0.03a 0.21±0.02ab 81.880 <0.001 1.38±0.14 1.30±0.12a 1.24±0.12ab 79.300 <0.001
脑损伤组 70 0.61±0.06 0.56±0.06a 0.48±0.05ab 88.240 <0.001 1.58±0.15 3.01±0.31a 1.46±0.15ab 177.900 <0.001
t值   0.536 24.944 41.948     8.156 43.039 9.580    
P值   <0.001 <0.001 <0.001     <0.001 <0.001 <0.001    
图1 血清Tau水平和TLR4水平预测早产儿脑损伤的ROC曲线A：Tau蛋白；B：TLR4蛋白；C：联合预测
表3 血清Tau和TLR4水平预测早产儿脑损伤的ROC曲线特征
指标 时间 AUC 95%CI P值
Tau 第1天 0.626 0.540~0.706 0.008
第3天 0.764 0.685~0.831 <0.001
第7天 0.819 0.745~0.879 <0.001
TLR4 第1天 0.582 0.496~0.665 <0.036
第3天 0.820 0.746~0.880 <0.001
第7天 0.787 0.710~0.852 <0.001
联合预测 第1天 0.639 0.553~0.718 0.003
第3天 0.930 0.874~0.966 <0.001
第7天 0.887 0.822~0.934 <0.001
表4 3组不同程度脑损伤BIPI患儿不同时期血清Tau和TLR4水平比较（ng/mL，±s）
组别 例数 Tau TLR4
第1天 第3天 第7天 F值 P值 第1天 第3天 第7天 F值 P值
轻度脑白质损伤组 22 0.52±0.14 0.45±0.12c 0.30±0.08cd 20.639 <0.001 1.39±0.56 1.95±0.21c 1.31±0.61cd 10.997 <0.001
中度脑白质损伤组 27 0.58±0.16a 0.56±0.11ac 0.46±0.07acd 7.859 0.001 1.52±0.89a 3.02±0.31ac 1.36±0.72acd 48.288 <0.001
重度脑白质损伤组 21 0.78±0.20ab 0.69±0.18abc 0.59±0.15abcd 5.997 0.004 1.92±0.56ab 4.93±0.51abc 1.86±0.85abcd 247.754 <0.001
F值   14.289 16.412 33.477     3.298 6.912 3.789    
P值   <0.001 <0.001 <0.001     0.043 0.002 0.028    
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