Objective To analyze the association of the expression levels of serum neurofilament protein (NFP) and nuclear factor-erythroid 2-related factor-2 (Nrf2) in neonates with asphyxia, in order to provide theoretical reference for the diagnosis of early brain injury in neonatal asphyxia. Methods From May 2019 to April 2021, 91 full-term neonates with asphyxia admitted to Department of Neonatology, the Second Clinical Medical College of Yangtze University were selected as study subjects, and were divided into mild asphyxia group (n=40) and severe asphyxia group(n=51) according to Apgar score and umbilical artery blood gas analysis. Besides, neonates were divided into brain injury group (n=36) and non-brain injury group (n=55) according to the results of head MRI examination. Meanwhile, 50 full-term neonates without history of asphyxia and hypoxia, neurological disease and intrauterine infection, who were delivered in the Obstetrics Department of this hospital, were enrolled into the control group. Enzyme-linked immunosorbent (ELISA) method was used to detect serum NFP and Nrf2 expression levels. Pearson analysis was used to analyze the correlation of serum NFP and Nrf2 levels of the neonates in brain injury group with the score of Neonatal Behavioral Neurological Assessment (NBNA). ROC curve was used to analyze the diagnostic value of serum NFP and Nrf2 levels in the diagnosis of early brain injury in neonatal asphyxia. Results Serum NFP and Nrf2 levels of newborns in the mild asphyxia group and severe asphyxia group were significantly higher than those of the control group, and the NBNA score was significantly lower than that of the control group (F=294.939, 208.932, 286.915, P<0.001). Compared with newborns in the mild asphyxia group, serum NFP and Nrf2 levels of the newborns in the severe asphyxia group were significantly higher, and the NBNA score of the newborns was significantly lower (P<0.001). The levels of serum NFP and Nrf2 in neonates of the brain injury group were significantly higher than those of the non-brain injury group, and the NBNA score was significantly lower than that of the non-brain injury group (t=12.841, 12.539, 14.248, P<0.001). Pearson correlation analysis showed that serum NFP and Nrf2 levels of neonates in the brain injury group were negatively correlated with NBNA score (r＝-0.527,-0.401, P<0.001). The sensitivity and specificity of serum NFP combined with Nrf2 in the diagnosis of early brain injury in neonatal asphyxia was 94.44% and 81.82%, respectively, and the area under the curve was 0.925. Conclusions Serum NFP and Nrf2 levels in neonates with asphyxia are higher, which are associated with early brain injury of neonatal asphyxia. The combined detection of serum NFP and Nrf2 has a higher diagnostic value for the early brain injury of neonatal asphyxia.
Key words
neurofilament protein /
nuclear factor-erythroid 2-related factor-2 /
neonatal asphyxia /
brain injury
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References
[1] 张洋, 王显赫, 吴祥红, 等. 血清Toll样受体4和NF-kB联合检测在早产儿脑损伤中的诊断价值研究[J]. 中国实验诊断学, 2019, 23(5):845-847.
[2] Alkholy UM, Abdalmonem N, Zaki A, et al. Early predictors of brain damage in full-term newborns with hypoxic ischemic encephalopathy[J]. Neuropsychiatr Dis Treat, 2017, 13(1):2133-2139.
[3] Gaetani L, Blennow K, Calabresi P, et al. Neurofilament light chain as a biomarker in neurological disorders[J]. J Neurol Neurosurg Psychiatry, 2019, 90(8):870-881.
[4] Kuhle J, Kropshofer H, Haering DA, et al. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response[J]. Neurology, 2019, 92(10):e1007-e1015.
[5] Uruno A, Matsumaru D, Ryoke R, et al. Nrf2 suppresses oxidative stress and inflammation in App knock-in alzheimer's disease model mice[J]. Mol Cell Biol, 2020, 40(6):1-24.
[6] 刘璐, 李丹, 刘囡, 等. 创伤性脑损伤后核因子E2相关因子2在星形胶质细胞中的表达[J]. 解剖学杂志, 2018, 41(5):540-543.
[7] 中华医学会围产医学分会新生儿复苏学组.新生儿窒息诊断的专家共识[J].中华围产医学杂志, 2016, 19(1):3-6.
[8] 陈娟, 庄伟雄, 罗树荣, 等.MRI评估新生儿窒息后脑损伤及预后的应用价值[J].中国实用医药, 2016, 11(17):12-14.
[9] 苏猛, 张星, 张雷. NLR、NBNA评分在新生儿窒息中的临床应用价值[J]. 国际检验医学杂志, 2020, 41(12):1505-1508.
[10] Verde F,Steinacker P, Weishaupt JH, et al. Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis[J]. J Neurol Neurosurg Psychiatry, 2019, 90(2):157-164.
[11] Wang P, Fan J, Yuan L, et al. Serumneurofilament light predicts severity and prognosis in patients with ischemic stroke[J]. Neurotox Res, 2020, 37(4):987-995.
[12] 黄冠芬, 黄润忠, 张金凤, 等. 神经元特异性烯醇化酶及神经丝蛋白在窒息新生儿血液中的动态变化及意义[J]. 广东医学, 2016, 37(22):3412-3414.
[13] Khalil M,Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders[J]. Nat Rev Neurol, 2018, 14(10):577-589.
[14] 张琛, 沈文娟. 血清神经丝蛋白-3及特异性烯醇化酶在急性缺血性脑卒中的变化及意义[J]. 医学临床研究, 38(2):189-191.
[15] Gao Y, Fu R, Wang J, et al. Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway[J]. Pharm Biol, 2018, 56(1):440-449.
[16] Warpsinski G, Smith MJ, Srivastava S, et al. Nrf2-regulated redox signaling in brain endothelial cells adapted to physiological oxygen levels: Consequences for sulforaphane mediated protection against hypoxia-reoxygenation[J]. Redox Biol, 2020, 37(1):1-11.
[17] Yang R, Song C, Chen J, et al.Limonin ameliorates acetaminophen-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1[J]. Phytomedicine, 2020, 69(1):1-40.
[18] 刘庆, 卢蓉, 郝莉霞. Nrf2基因对缺氧缺血性脑损伤新生大鼠脑组织氧化应激和JAK2/STAT3信号通路的影响[J]. 局解手术学杂志, 2020, 29(8):604-609.
[19] 张海燕, 乔林霞, 朱文英, 等. NBNA评分联合头颅MRI在新生儿重度高胆红素血症脑损伤中的诊断价值[J]. 中国儿童保健杂志, 2017, 25(2):164-166.
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