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血清τ蛋白作为评估创伤性脑损伤的潜在生物标志物。

Serum τ protein as a potential biomarker in the assessment of traumatic brain injury.

作者信息

Wang Junwen, Li Jun, Han Lin, Guo Songbo, Wang Lei, Xiong Zuojun, Chen Zhi, Chen Wen, Liang Jian

机构信息

Department of Neurosurgery, Wuhan Central Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

Department of Neurosurgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

出版信息

Exp Ther Med. 2016 Mar;11(3):1147-1151. doi: 10.3892/etm.2016.3017. Epub 2016 Jan 22.

Abstract

Traumatic brain injury (TBI) is the leading cause of mortality and disabilities among all trauma cases. Following TBI, damage to axons results in τ protein hyperphosphorylation leading to microtubule instability and τ-mediated neurodegeneration. In addition, τ protein is proteolytically cleaved and is able to access the cerebrospinal fluid (CSF) and serum; thus, this protein may serve as a potential biomarker in the diagnosis of injury severity and outcome prediction. Although a limited number of studies have investigated the CSF τ protein levels after TBI, the data are divergent and conflicting, and investigations into the serum τ protein levels have yet to be conducted. Therefore, the present study aimed to examine the serum τ protein levels in the full spectrum of TBI patients on days 0-14 after TBI, using an enzyme-linked immunosorbent assay. The protein levels were compared to the initial Glasgow Coma Score (GCS) and the Extended Glasgow Outcome Scale (GOS-E), which are used to represent the injury severity and patient outcome, respectively. In total, 56 patients, including 20 patients with mild TBI (GCS, 13-15), 19 patients with moderate TBI (GCS, 9-12) and 17 patients with severe TBI (GCS, 3-8), were included in the current study. The outcome was assessed 1 year after the injury and patients were classified into the good outcome (40 cases; GOS-E, 5-8) and poor outcome groups (16 cases; GOS-E, 1-4). The results indicated that serum τ protein levels increased soon after TBI and reached a peak value at ~2 days after the injury. The serum τ protein levels were significantly higher in the severe TBI group compared with those in the mild and moderate TBI groups (P<0.0001). Univariate analysis indicated that poor outcome was significantly associated with higher serum τ protein levels on day 2 (P<0.0001). A receiver operating characteristic curve demonstrated that a τ protein level of >116.04 pg/ml on day 2 resulted in a 93.75% sensitivity and 92.50% specificity for predicting a poor outcome. Furthermore, a τ protein level of >372.1 pg/ml on day 2 yielded 100% sensitivity and 83.33% specificity for 1 year mortality in the severe TBI group. In conclusion, the present study suggests that serum τ protein may serve as a potential biomarker for evaluating the injury severity and predicting the outcome of TBI patients.

摘要

创伤性脑损伤(TBI)是所有创伤病例中导致死亡和残疾的主要原因。TBI后,轴突损伤导致τ蛋白过度磷酸化,进而导致微管不稳定和τ介导的神经退行性变。此外,τ蛋白被蛋白水解切割后能够进入脑脊液(CSF)和血清;因此,这种蛋白可能作为评估损伤严重程度和预测预后的潜在生物标志物。尽管已有少数研究调查了TBI后脑脊液中τ蛋白水平,但数据存在分歧和冲突,且尚未对血清τ蛋白水平进行研究。因此,本研究旨在采用酶联免疫吸附测定法检测TBI患者伤后0 - 14天内血清τ蛋白水平。将蛋白水平与分别代表损伤严重程度和患者预后的初始格拉斯哥昏迷评分(GCS)及扩展格拉斯哥预后量表(GOS - E)进行比较。本研究共纳入56例患者,其中轻度TBI患者20例(GCS,13 - 15),中度TBI患者19例(GCS,9 - 12),重度TBI患者17例(GCS,3 - 8)。在伤后1年评估预后,并将患者分为预后良好组(40例;GOS - E,5 - 8)和预后不良组(16例;GOS - E,1 - 4)。结果表明,TBI后血清τ蛋白水平迅速升高,并在伤后约2天达到峰值。重度TBI组血清τ蛋白水平显著高于轻度和中度TBI组(P<0.0001)。单因素分析表明,伤后第2天预后不良与血清τ蛋白水平升高显著相关(P<0.0001)。受试者工作特征曲线显示,伤后第2天τ蛋白水平>116.04 pg/ml时,预测预后不良的敏感性为93.75%,特异性为92.50%。此外,重度TBI组伤后第2天τ蛋白水平>372.1 pg/ml时,预测1年死亡率的敏感性为100%,特异性为83.33%。总之,本研究表明血清τ蛋白可能作为评估TBI患者损伤严重程度和预测预后的潜在生物标志物。

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