Expression and significance of miR-124, NSE and S100B in neonatal hypoxic-ischemic encephalopathy
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摘要:
目的 检测新生儿缺氧缺血性脑病(HIE)中枢神经特异性蛋白(S100B)、神经元特异性烯醇化酶(NSE)和miR-124的表达水平，并探究其辅助诊断的价值。 方法 选取2020年12月—2021年12月蚌埠医学院第一附属医院HIE患儿50例(HIE组)，同期出生的健康新生儿50例(健康组)，均于生后2 h内采集脐带血，采用实时荧光定量(qRT-PCR)法检测miR-124水平，并于生后6 h内采集新生儿股静脉血，采用ELISA方法检测S100B、NSE表达水平，建立受试者操作特征(ROC)曲线，评估上述生物标志物在HIE中的临床意义。 结果 与健康新生儿比较，HIE患儿的miR-124表达水平降低(0.63±0.11 vs. 0.90±0.22)，S100B和NSE水平显著增高[0.45(0.34，0.78)μg/L vs. 0.33(0.24，0.50)μg/L，39.30(23.71，67.48)μg/L vs. 21.16(16.27，27.25)μg/L]，差异均有统计学意义(均P < 0.05)，且不同程度HIE患儿miR-124、S100B、NSE比较差异均有统计学意义(均P < 0.05)。ROC分析结果显示血清miR-124、S100B、NSE诊断HIE的曲线下面积AUC分别为0.897、0.690、0.801，miR-124、S100B和NSE联合检测诊断HIE的AUC为0.908，诊断效能最佳。HIE新生儿行为神经评估(NBNA)评分与S100B、NSE呈负相关关系，与miR-124呈正相关关系。 结论 HIE新生儿脐带血中miR-124表达水平降低，miR-124联合S100B及NSE对HIE的诊断价值较高。 -
关键词:
- MiR-124 /
- 新生儿缺氧缺血性脑病 /
- 神经元特异性烯醇化酶 /
- 中枢神经特异性蛋白
Abstract:Objective To investigate the expression levels of central neuron-specific protein (S100B), neuron-specific enolase (NSE) and miR-124 in neonatal hypoxic-ischemic encephalopathy (HIE) and to explore their diagnostic value. Methods A total of 100 full-term neonates in the First Affiliated Hospital of Bengbu Medical College from December 2020 to December 2021 were selected, including 50 neonates in the HIE group and 50 neonates in the healthy group. Umbilical cord blood was collected within 2 hours after birth, and the level of miR-124 was detected by real-time fluorescence quantification PCR (qRT-PCR); and femoral vein blood was collected from neonates within 6 hours after birth to detect S100B and NSE levels by ELASA, and the receiver operating characteristic (ROC) curve was constructed to evaluate the clinical significance of the above biomarkers in HIE. Results Compared to healthy neonates, the expression level of miR-124 was decreased in neonates with HIE (0.63±0.11 vs. 0.90±0.22), whereas the levels of S100B and NSE were significantly increased [0.45 (0.34, 0.78) μg/L vs. 0.33 (0.24, 0.50) μg/L, 39.30 (23.71, 67.48) μg/L vs. 21.16 (16.27, 27.25) μg/L], the differences were statistically significant (all P < 0.05), and there were statistically significant differences in miR-124, S100B and NSE in neonates with different HIE levels (all P < 0.05). ROC analysis results showed that the area under the curve AUCs of serum miR-124, S100B and NSE for HIE diagnosis were 0.897, 0.690 and 0.801, respectively, and the AUC of combined detection of miR-124, S100B and NSE for HIE diagnosis was 0.908, indicating the best diagnostic efficiency. The Neonatal Behavioral Neurological Assessment (NBNA) score of HIE was negatively correlated with S100B and NSE, and positively correlated with miR-124. Conclusion The expression level of miR-124 in umbilical cord blood of neonates with HIE is decreased, and miR-124 combined with S100B and NSE is of high diagnostic value for HIE. -
Key words:
- MiR-124 /
- Neonatal hypoxic-ischemic encephalopathy /
- Neuron specific enolase /
- S100B
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图 1 S100B、NSE和miR-124诊断HIE新生儿的ROC曲线
Figure 1. ROC curves of S100B, NSE, and miR124 for the diagnosis of HIE in neonates
表 1 引物序列
Table 1. Primer sequences
引物 正向序列5′-3′ 反向序列5′-3′ miR-124 UAAGGCACGCGGUGAAUGCC UAAGGCACGCGGUGAA U6 AGAGAAGATTAGCATGGCCCCTG ATCCAGTGCAGGGTCCGAGG 
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表 2 2组新生儿一般基线资料比较
Table 2. Comparison of general baseline data of neonates between the two groups
组别 例数 性别(例) 分娩方式(例) 胎龄
(x±s，周)出生体重
(x±s，g)男 女 顺产 剖宫产 健康组 50 38 12 23 27 38.24±1.36 3 028±569 HIE组 50 34 16 15 35 38.28±1.41 2 857±714 统计量 0.794a 2.689a 0.144b 1.318b P值 0.373 0.101 0.886 0.190 注：a为χ2值，b为t值。
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表 3 HIE与健康组新生儿S100B、NSE和miR-124表达水平比较(x±s)
Table 3. Comparison of S100B, NSE and miR124 expression levels in HIE and healthy neonates(x±s)
组别 例数 NSE(μg/L) S100B(μg/L) miR-124 健康组 50 21.16(16.27，27.25) 0.33(0.24，0.50) 0.90±0.22 HIE组 50 39.30(23.71，67.48) 0.45(0.34，0.78) 0.63±0.11 统计量 -5.184a -3.282a 7.644b P值 < 0.001 0.001 < 0.001 注：a为Z值，b为t值。
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表 4 不同程度HIE新生儿S100B、NSE、miR-124表达水平比较(x±s)
Table 4. Comparison of S100B, NSE, and miR124 expression levels in neonates with different degrees of HIE(x±s)
组别 例数 NSE(μg/L) S100B(μg/L) miR-124 轻度组 35 32.55±13.51 0.38±0.09 0.68±0.05 中度组 9 73.95±15.21a 0.83±0.14a 0.55±0.04a 重度组 6 104.59±6.34ab 1.35±0.22ab 0.39±0.03ab F值 95.619 177.471 103.712 P值 < 0.001 < 0.001 < 0.001 注：与轻度组比较, aP < 0.01；与中度组比较, bP < 0.01。
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表 5 NSE、S100B、miR-124在HIE中的诊断价值
Table 5. Diagnostic value of NSE, S100B, and miR124 in HIE
指标 AUC 截断值 灵敏度
(%)特异度
(%)95% CI NSE 0.801 23.165 84.0 65.3 0.715~0.886 S100B 0.690 0.395 66.0 70.0 0.587~0.794 miR-124 0.897 0.777 98.0 80.0 0.827~0.966 NSE+S100B+miR-124 0.908 90.0 86.0 0.846~0.970
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表 6 NSE、S100B、miR-124与HIE新生儿NABA评分的相关性
Table 6. Correlation between NSE, S100B, miR124 and NABA score in neonates with HIE
指标 NABA评分 r值 P值 NSE -0.758 < 0.001 S100B -0.747 < 0.001 miR-124 0.652 < 0.001
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