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弥漫性轴突损伤患者血清S100B和神经元特异性烯醇化酶的变

发表时间:2011-08-19  浏览次数:501次

  作者:顾建军,鲁峻,高广忠,张勤,蒋霖  作者单位:江苏省泰州市人民医院神经外科, 泰州

  【摘要】 目的:探计弥漫性轴突损伤(diffuseaxonalinjury, DAI)患者血清S100B和神经元特异性烯醇化酶(neuron specifis enolase,NSE)浓度的变化及临床意义。方法:选择符合DAI诊断标准的脑外伤患者46例,对照组为同期受伤20例单纯头皮挫裂伤,无失血性休克患者.按照格拉斯哥预后评分Ⅰ~Ⅲ级(死亡,植物生存,严重残残)为预后不良组18例;Ⅳ-Ⅴ级(轻-中度致残和完全恢复)为预后良好组28例;于损后1h,3h,6h,12h,24h和48h采血检测血清中S100B和NSE浓度。结果:与对照组比较,DAI组S100B蛋白在伤后1h就明显增高(P<0.01),并持续升高至伤后6h,但预后良好组12~24h有所下降(P>0.05),48h下降有统计学意义(P<0.05);预后不良组S100B蛋白持续不下降。而NSE于伤后3h开始升高(P<0.05),6h达高峰(P<0.01),预后良好组12h下降(P<0.01),24h降至正常;预后不良组NSE持续不下降。结论:DAI患者血清S100B蛋白和NSE含量明显升高,联合监测血清S100B和NSE蛋白含量的变化不但能准确地反映出脑损害和程度而且可以判断DAI的预后。

  【关键词】 弥漫性轴突损伤; S100B;神经元特异性烯醇化酶;酶联免疫吸附试验

  Changes of serum neuron-specific enolase(NSE) and S100B in head trauma patients with diffuseaxonalinjury(DAI) and their clinical significance GU Jianjun, LU Jun, GAO Guangzong, et al (Department of Neurosurgery, Taizhou People′s Hospital, Taizhou 225300)

  [Abstract] Objective: To investigate the changes of serum neuron-specific enolase (NSE) and S100B in head trauma patients with diffuseaxonalinjury(DAI) and their clinical significance. Mehtods:Forty-six cases of DAI were selected according to diagnostic criteria of DAI. The control group contained 20 cases with simple scalp lacerated wound,and none of them had hemorrhagic shock.The prognosis of 18 patients with Ⅰ~Ⅲ of Glasgow prognosis score(died, plant status and serious mutilation) was considered unfavourable,and the the prognosis of 28 patients with Ⅳ~Ⅴ(middle to moderate mutilation or complete recovery) was considered favourable.The levels of NSE and S100 B in all patients were detected at hours 1,3,6,12, 24 and 48 after trauma. Results: The levels of S100B were obviously higher in the group of DAI ,compared with control group at 1 hour following head trauma (P<0.01), and continuely higher within 6 h, but the levels of S100B were decreased in patients with well prognosis(P>0.05) and they presented statistical significance at 48 h.The levels of S100B in patients with bad prognosis were not decreased,and the levels of NSE were obviously higher at 3 h following head trauma(P<0.05),which peaked at 6 h (P<0.01),while in patients with well prognosis the levels of NSE were decreased at 12 h following head trauma (P<0.01) and they reached normal level at 48 h. The levels of NSE in patients with bad prognosis were not decreased. Conclusion: The levels of NSE and S100B in serum are elevated obviously in head trauma patients with DAI. Monitoring the changes of NSE and S100B combinatively may not only reflect the severity of brain damage exactly,but also predict the prognosis of patients with DAI.

  [Key Words] Diffuseaxonalinjury; S100B; Neuron specific enolase; Enzyme-linked immunosorbent assay

  弥漫性轴突损伤(diffuseaxonalinjury,DAI)作为脑原发性损伤的一种重要类型,是决定脑外伤患者临床状况和预后的重要因素之一。由于DAI的症状及体征缺乏特异性,需要对脑细胞损伤进行直接定量评估,为临床评估DAI脑损害的程度和预后判断提供依据。

  现有较多反映脑损害的神经生物化学物质如S100B和神经元特异性烯醇化酶(NSE)等。当中枢神经系统病变或外伤受损时,在受损组织、血清及脑脊液中均可检测到S100B和NSE蛋白,但针对DAI这方面的标志物研究甚少,本研究通过DAI患者早期血清S100B和NSE深度的测定,探讨DAI患者脑损害程度及血清S100B和NSE深度之间的关系,为临床监测脑外伤患者的病情、评估其预后提供依据。

  1 资料方法

  1.1 仪器与试剂 采用ELISA测定S100B浓度(武汉博士德)和NSE深度(CanAg公司),检测仪器采用BioRad酶标仪和自动洗板机。

  1.2 资料和方法 本组男26例,女20例,好发年龄18~40岁。车祸伤35例,高处坠落伤13例。入院时全部为昏迷状态,GCS 3~12分。CT表现:脑肿胀,脑室和脑池受压变小。脑白质与脑灰质交界处散在,不对称密度小出血点和蛛网膜下腔出血或硬膜下薄层血肿。MRI的表现T2加权见脑白质、脑灰质交界处和胼胝体散在,分布不对称,圆形或不规则异常高信号。患者伤后1、3、6、12、24、48 h抽取肘静脉血2 ml,2000 r/min 离心5 min,取血清,置-70℃备检。对照组样品保存及测定方法与病例组相同。S100B和NSE按试剂盒说明书进行操作。

  1.3 统计学方法 所测数据用表示,采用t检验。

  2 结 果

  与对照组相比, DAI组S100B蛋白在伤后1 h就明显增高(P<0.01),并持续升高至伤后6h,但预后良好组12~24 h有所下降(P>0.05),48 h明显下降(P>0.05);预后不良组S100B蛋白持续不下降。而NSE于伤后3 h开始升高(P>0.05),6 h达高峰(P<0.01),预后良好组12 h下降(P<0.01),24 h降至正常;预后不良组持续不下降。

  3 讨 论

  目前对弥漫性轴突损伤原发性脑损害的评估及预后的早期评估主要依赖伤后临床表现(如GCS)及影像学表现(如头颅CT)等间接手段,而缺乏对脑细胞损伤进行定量评估的直接手段,给临床救治效果的评估及有关研究造成一定困难。而S100B蛋白是一种分子量为21kD的酸性蛋白,由2个β亚单位组成的二聚体,其生物半衰期为2 h,通过肾脏代谢和清除。它在脑组织中含量丰富(3500 ng/mg蛋白),远高于其他组织(100~200 ng/mg蛋白),具有广泛的生物学活性,在细胞增生、分化、基因表达、细胞凋亡中发挥重要作用。正常情况下,S100B蛋白不能通过血脑屏障,颅脑损伤后脑组织的损伤直接导致脑细胞和血脑屏障的破坏,使血S100B蛋白迅速升高,故可作为中枢神经系统疾病的生化检测标志物[1]。S100B蛋白血清水平越高,脑损害越严重,预后越差。Ingebrigtsen等[2]发现,伤后2~6 h内测到的血清S100B蛋白水平最能反映出原发性脑损害,而12 h后S100B蛋白的升高表明胶质细胞功能障碍或/和持续死亡引起的迟发性或进行性释放。Raabe等[3]认为,颅脑损伤12 h后测到的血S100B蛋白具有更高的特异性和阳性预示值,更能反映出原发性损伤或进行性继发性脑损害的严重程度。本文结果提示预后良好组S100B含量在48 h内降至正常水平,说明脑细胞处于稳定状态,神经功能恢复较好;预后不良组S100B含量持续不降或增高提示有进展性脑损害,神经功能恢复差。

  NES是主要存在于神经元细胞中的一种可溶性胞浆蛋白,是烯醇化酶的二聚体同工酶。急性颅脑损伤时,大量神经元细胞受到创伤损坏,神经元特异性烯醇化酶被释放出细胞外,同时血脑屏障遭到破坏,神经元特异性烯醇化酶透过受损的血脑屏障进入血循环/致血清中神经元特异性烯醇化酶水平升高。脑损伤程度越重,死亡崩解的神经元越多,血脑屏障受到损害的程度越高/神经元释放入血的神经元特异性烯醇化酶越多[4]。 Ruchem等报道,脑外伤后血清NSE浓度与预后直接相关,认为伤后血清NSE浓度与临床表现相结合可为评估预后提供定量方法[5]。本文结果NSE于伤后1 h的NSE水平差异无显著性(P>0.05),3 h开始升高,6 h达高峰,预后良好组12 h下降,24 h降至正常;而预后不良组持续升高(P<0.01)。

  本研究显示,在所有DAI患者外伤后早期,即使CT扫描检查阴性,血清S100B、NSE值均有明显升高,并且在DAI预后不良组伤后血清S100B、NSE浓度均显著高于预后良好组,而且其浓度持续不降或增高。提示血清S100B、NSE浓度可以反应DAI不同程度的脑损害,为临床上直接通过检测外周血清中的S100B、NSE浓度评估颅脑损伤程度及预后提供了可靠依据。

  【参考文献】

  [1] 徐卫平,谢 飞,朱忠勇.S100B蛋白的检测及其临床应用[J].国外医学•临床生物化学与检验学分册,2001,22(4):173-174.

  [2] Ingebrigtsen T, Romner B. Serial S-100 protein serum measurements related to early magnetic resonance imaging after minor head injury case report[J]. J Neurosurg. 1996,85(5):945-948.

  [3] Raabe A, Grolms C, Serfert V. Serum markers of brain damage and out come prediction in patients after severe head injury[J]. Br J Neurosurg, 1999,13(1):55-59.

  [4] Skogseid IM, Nordby HK, Urdal P,et al.Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage[J]. Acta Neurochir(Wien),1992,115(3-4):106-111.

  [5] Ruchem E,Ugur B,Gokhan A,et al.Prognostic value of neuron specific enolase levels after head injury[J].Neurol Res,1998,20(5):418-420.

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