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实验性急性脊髓损伤的血清生物标志物:神经元特异性烯醇化酶和S-100β迅速升高。

Serum biomarkers for experimental acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100beta.

作者信息

Loy David N, Sroufe Angela E, Pelt Jennifer L, Burke Darlene A, Cao Qi-Lin, Talbott Jason F, Whittemore Scott R

机构信息

Kentucky Spinal Cord Injury Research Center, and Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.

出版信息

Neurosurgery. 2005 Feb;56(2):391-7; discussion 391-7. doi: 10.1227/01.neu.0000148906.83616.d2.

DOI:10.1227/01.neu.0000148906.83616.d2
PMID:15670387
Abstract

OBJECTIVE

We evaluated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein are biomarkers for traumatic injury in an animal model of spinal cord injury (SCI).

METHODS

Enzyme-linked immunosorbent assay serum measurements of NSE and S-100beta and assays of serum protein were compared at 6 and 24 hours after a graded contusive SCI (150 or 200 kdyn IH impactor injury (Infinite Horizons, L.L.C., Lexington, KY) or sham laminectomy at T9 in 30 female Sprague-Dawley rats. Serum from control animals was also analyzed.

RESULTS

Increases in serum levels of NSE were observed for 200-kdyn (3.1-fold, P < 0.001) and 150-kdyn (2.3-fold, P < 0.001) injury groups at 6 hours after injury, which decreased by 73.7% (P < 0.001) and 65.2% (P < 0.001) at 24 hours after SCI, respectively; the levels were still greater than in sham animals (P < 0.001, P = 0.001). The 200- and 150-kdyn injury groups were not different at either time point. S-100beta serum levels increased at 6 hours in the 200-kdyn injury group (P < 0.05), and no differences from sham levels were seen at 24 hours. No differences in total protein concentrations were observed between the injury and control groups.

CONCLUSION

Present data suggest that NSE and S-100beta serum levels may be useful experimental tools for the acute measurement of tissue loss after SCI. Despite significant shortcomings, NSE and S-100beta serum measurements in acute SCI patients with clinically defined functional deficits should allow comparisons with well-characterized SCI animal models. Future efforts to develop biomarkers that predict functional outcomes in the acute phase should focus on axon-specific proteins as markers of secondary axonal loss and regeneration.

摘要

目的

我们评估了在脊髓损伤(SCI)动物模型中,血清神经元特异性烯醇化酶(NSE)和S-100β蛋白水平是否为创伤性损伤的生物标志物。

方法

在30只雌性Sprague-Dawley大鼠中,于分级挫伤性SCI(150或200千达因IH撞击伤(Infinite Horizons, L.L.C., 肯塔基州列克星敦))或T9节段假椎板切除术后6小时和24小时,比较NSE和S-100β的酶联免疫吸附测定血清测量值以及血清蛋白测定值。还分析了对照动物的血清。

结果

在损伤后6小时,200千达因(3.1倍,P < 0.001)和150千达因(2.3倍,P < 0.001)损伤组的血清NSE水平升高,在SCI后24小时分别下降了73.7%(P < 0.001)和65.2%(P < 0.001);这些水平仍高于假手术动物(P < 0.001,P = 0.001)。200千达因和150千达因损伤组在两个时间点均无差异。200千达因损伤组的S-100β血清水平在6小时时升高(P < 0.05),在24小时时与假手术水平无差异。损伤组和对照组之间未观察到总蛋白浓度的差异。

结论

目前的数据表明,NSE和S-100β血清水平可能是急性测量SCI后组织损伤的有用实验工具。尽管存在显著缺点,但对具有临床定义功能缺陷的急性SCI患者进行NSE和S-100β血清测量应能与特征明确的SCI动物模型进行比较。未来开发预测急性期功能结局的生物标志物的努力应集中于轴突特异性蛋白,将其作为继发性轴突损失和再生的标志物。

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