颅脑损伤患者早期缺血修饰白蛋白的检测

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邹国英, 任碧琼. 颅脑损伤患者早期缺血修饰白蛋白的检测. 2013, 28(2): 93-96
ZOU Guoying, REN Biqiong. Detection of serum ischemia-modified albumin in patients with early traumatic craniocerebral injury. Labratory Medicine, 2013, 28(2): 93-96 复制到剪切板

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颅脑损伤患者早期缺血修饰白蛋白的检测

邹国英, 任碧琼

湖南省第二人民医院检验科,湖南长沙 410007

作者简介：邹国英,女,1975年生,硕士,主管技师,主要从事临床生物化学与分子生物学检验工作。

基金:湖南省第二人民医院临床重点建设专科资助项目(2012);

摘要

目的

研究颅脑损伤患者早期血清缺血修饰白蛋白 (IMA) 水平的动态变化及临床意义。

方法

将90例颅脑损伤患者按照格拉斯哥昏迷记分法(GCS)评分分为轻度损伤(13~15分)组(29例)、中度损伤(9~12分)组(29例)、重度损伤(3~8 分)组(32例),将36名健康体检者设为正常对照组。测定颅脑损伤患者伤后3、6、12、24、48、72 h及正常对照组血清IMA、C反应蛋白(CRP)、髓过氧化物酶(MPO)水平。

结果

不同损伤程度的颅脑损伤患者伤后3~72 h血清IMA水平均高于正常对照组(P<0.01);且随着损伤程度的加重而增高,轻度损伤组低于中、重度损伤组(P<0.01)。不同损伤程度患者血清IMA水平在早期不受病情进程的影响(P>0.10),与CRP、MPO存在正相关。

结论

颅脑损伤患者早期氧缺乏和炎症反应的存在引起IMA持续增高,且与病情的严重程度呈正相关,对病情的评估、继发性脑损伤及治疗有指导作用。

关键词: 缺血修饰白蛋白; 颅脑损伤; C反应蛋白; 髓过氧化物酶

中图分类号:R446.1 文献标志码:A 文章编号:1673-8640(2013)02-0093-04

Detection of serum ischemia-modified albumin in patients with early traumatic craniocerebral injury

ZOU Guoying, REN Biqiong

Department of Clinical Laboratory, Hunan Second People's Hospital, Hunan Changsha 410007, China

Abstract

Objective

To research the dynamic changes and clinical significance of serum ischemia-modified albumin (IMA) in patients with early traumatic craniocerebral injury.

Methods

A total of 90 patients with traumatic craniocerebral injury were classified into 3 groups according to the Glasgow Coma scale (GCS) scores [score 13-15: mild injury group (29 cases), score 9-12: medium injury group (29 cases) and score 3-8: severe injury group (32 cases)], and 36 healthy subjects were enrolled as healthy controls. The levels of serum IMA, C reactive protein (CRP) and myeloperoxidase (MPO) were determined in patient group at 3, 6, 12, 24, 48 and 72 h after injury and in healthy control group.

Results

The levels of serum IMA at 3-72 h after injury in patients with traumatic craniocerebral injury were significantly higher than those in healthy control group (P<0.01) and increased with the degree of injury, and the levels of serum IMA in mild injury group were lower than those in medium and severe injury groups (P<0.01). The levels of serum IMA in early injury had no change with the development of the disease(P>0.10), and there was a positive correlation with CRP and MPO.

Conclusions

The levels of serum IMA are significantly increasing continuously because of oxygen lack and inflammation reaction in patients with early traumatic craniocerebral injury, and are related positively with the severity of disease. IMA has the significance for the severity evaluation, secondary craniocerebral injury and therapy in patients with early traumatic craniocerebral injury.

Keyword: Ischemia-modified albumin; Traumatic craniocerebral injury; C reactive protein; Myeloperoxidase

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引言

缺血修饰白蛋白(ischemia-modified albumin,IMA)是指因组织缺血导致其氨基末端序列因受到缺血产生的自由基等的修饰,而与某些过渡金属的结合能力减低^{[ 1]}的白蛋白。David Bar-or首先报道急性冠状动脉综合征患者血清白蛋白结合外源性钴(Co²⁺)的能力降低,利用白蛋白-钴结合(albumin cobalt binding,ACB)试验测定IMA,并用于心肌缺血检测。目前已有许多相关的研究展开,但国内、外都很少有IMA与颅脑损伤方面相关的报道。我们研究观察了颅脑损伤早期IMA的动态变化,探讨其与颅脑损伤程度的关系及临床意义。

材料和方法

一、研究对象

选取2007年10月至2008年5月在湖南省第二人民医院创伤脑外科住院的患者90例,男62例,女28例,年龄3~80岁。入选标准:患者经CT扫描发现原发和(或)继发颅脑损伤,排除严重合并伤者。所有患者均符合颅脑损伤诊断标准。患者均为12 h内住院,排除糖尿病、高脂血症、高血压及肝、肾、心血管疾病。按GCS评分将患者分为轻度损伤(13~15 分)组29例、中度损伤(9~12分)组29例、重度损伤(3~8 分)组32例。正常对照者为健康体检者36名,男24名,女12名,年龄22~61岁,血常规、血糖、糖化血红蛋白(CHbA_1c)、血脂及肝、肾、心功能检查正常,排除肝、肾、心血管疾病及近期感染。

二、方法

1.样本采集

受检者于伤后3 h内采集第1次样本,取肘静脉血3 mL,其后6、12、24、48、72 h各采集1次,无抗凝剂样本1 500× g离心10 min,取血清-80 ℃保存,用于IMA、髓过氧化物酶(MPO)、C反应蛋白(CRP)检测。

2.IMA测定

试剂盒由长沙颐康科技开发有限公司提供,在德国西门子拜耳ADVIA 1650全自动生化分析仪上测定。反应原理:血清中白蛋白与Co²⁺结合后剩余的游离Co²⁺与有机显色物反应生成红褐色产物,在510 nm波长下比色,其吸光度值与Co²⁺水平成正比。与标准品进行比较,即可计算出样本中ACB的浓度,结果由ACB单位表示。单位定义:1 mL 血清中的白蛋白在510 nm波长下吸附1 μg Co²⁺为1 个单位(U/mL)。通过测定与白蛋白结合的Co²⁺间接反映IMA 水平,不同于使用抗体直接测定IMA。在缺血时,与Co²⁺结合的白蛋白减少,吸附结合的Co²⁺减少,ACB 测定值即降低,反而表明体内IMA升高。

3.MPO测定

试剂盒由南京建成生物工程研究所提供,用日本岛津UV-2501PC紫外分光光度计比色测定。

4.CRP测定

CRP用免疫比浊法,试剂盒由宁波美康公司提供试,在德国西门子拜耳ADVIA 1650全自动生化分析仪上测定。

三、统计学方法

统计软件为EXCEL和SPSS 16.0。检测结果以 ±s表示。多组之间比较用方差分析(ANOVA)的Games-Howell检验, P<0.05表示差异有统计学意义。相关性分析采用Pearson相关分析。

一、颅脑损伤患者IMA水平的变化

不同损伤程度的颅脑损伤患者伤后3~72 h内血清IMA水平均高于正常对照组( P<0.01)。颅脑损伤患者血清IMA水平随损伤程度加重而增高,中、重度损伤组IMA水平明显高于轻度损伤组( P<0.01),见表1。

表1 颅脑损伤组及正常对照组ACB测定值的变化(

)

二、不同程度颅脑损伤患者血清IMA水平动态观察

不同损伤程度血清IMA水平不受病情进程的影响( P>0.10),在损伤早期不随病情发展而变化,见图1。

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	图1 不同程度颅脑损伤患者血清IMA水平动态观察

三、颅脑损伤患者血清IMA水平与炎症指标的相关性分析

血清IMA水平与单个炎症指标分别分析时,颅脑损伤患者ACB值与CRP、MPO存在负相关( r值分别为-0.118、-0.165),即血清IMA水平与CRP、MPO存在正相关( P值分别0.044、0.005)。

讨论

IMA也称钴结合蛋白。当组织缺血缺氧时,组织细胞进行无氧代谢,乳酸增加,局部微环境pH值下降,在维生素C的作用下,Cu²⁺被还原为Cu⁺,与氧反应生成超氧自由基,被组织中的的超氧化物歧化酶(SOD)催化生成过氧化氢(H₂O₂)和氧气。正常情况下,H₂O₂由过氧化物酶降解成水和氧气,是无害的;而当有Cu²⁺存在时,可通过Fenton反应形成羟自由基(·OH)。易损害人血清白蛋白,使N 末端序列的2~4个氨基酸发生改变,形成IMA。IMA与Co²⁺的结合能力下降,临床上利用ACB试验检测IMA水平。

目前大多认为IMA是急性缺血事件和诊断ACS的有用指标,与肌钙蛋白联用对胸痛患者的诊断和处理更有价值^{[ 2]},对于鉴别心肌梗死更优于CRP^{[ 3]},总体效果可与肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)相当^{[ 4]}。然而,新近的调查研究表明IMA不仅仅是心肌缺血的标志物。Gunduz 等^{[ 5]}发现脑血管疾病患者的IMA 水平较高,并可用于鉴别蛛网膜下腔出血和脑栓塞。本研究表明颅脑损伤患者IMA水平升高,可能为颅脑局部组织损伤缺血缺氧,启动白蛋白的氧化修饰。颅脑损伤时,外力使颅内微血管受到冲击、震动,甚至撕裂,导致血管内皮失去连接而脱落。颅内微血管受到损伤,导致脑组织缺血缺氧,形成微小的梗死灶,诱导血清白蛋白的氧化修饰。损伤越严重,氧化修饰越显著,表现为IMA水平的增加越突出,与颅脑损伤的程度正相关,这与国外的一些研究结果也一致。Abboud等^{[ 6]}发现在脑梗死和脑出血患者比一过性脑缺血患者发作初期IMA水平明显增高,且发病后第1个24 h内脑梗死患者IMA水平逐渐升高而脑出血患者无明显变化,认为血清IMA水平与疾病程度相关,可作为早期鉴别急性脑卒中的生化标志物。本研究中重度与中度损伤组IMA并无差异,可能是重度损伤患者入院后很快死亡而无法入组,存活的重度组均表明病情得到有效控制,故与中度损伤组差异不明显。

IMA作为氧化应激的标志物可用来检测任何缺血事件,Falkensammer等^{[ 7]}选择健康者进行平板试验,结果显示袖带放开30min内血清IMA明显升高,30 min后恢复至基线水平。Piwowar等^{[ 8]}研究发现,高血糖和氧化应激引起的慢性缺氧使糖尿病患者的IMA 升高,并且IMA与HbA_1c有明显的相关性。但本研究结果并不是单纯的氧化应激反应所致,在颅脑损伤的3 h内IMA就迅速升高;在72 h内,不管病情的进展如何,IMA均维持在一个稳定的较高水平。这应是局部组织缺氧的微环境所致。有研究^{[ 9, 10]}发现炎症标志物MPO、CRP表达增高,且与IMA呈正相关。表明氧缺乏和炎症反应的存在引起IMA的持续增高。在糖尿病患者的研究中也发现各种氧化及炎症标志物如高敏CRP、氧化修饰低密度脂蛋白(ox-LDL)、抗-oxLDL、白细胞介素-6(IL-6)与IMA一样均升高^{[ 11]}。

综上所述,颅脑损伤患者存在局部缺氧的微环境,氧化应激和炎症反应引起血清IMA水平升高,且与病情的严重程度呈正相关。这对病情的评估、继发性颅脑损伤及治疗方案的选择有一定的指导作用。最近研究显示在终末期肾病患者,血清IMA水平能预测心血管疾病的死亡率^{[ 12]},本研究颅脑损伤患者的损伤早期虽然与病程发展无关,但延长监测时间是否与预后有关,或是与死亡率有关,还值得进一步的调查。

The authors have declared that no competing interests exist.

参考文献

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2003

0.0

... 引言缺血修饰白蛋白(ischemia-modified albumin,IMA)是指因组织缺血导致其氨基末端序列因受到缺血产生的自由基等的修饰,而与某些过渡金属的结合能力减低^[1]的白蛋白 ...

2008

0.956

0.0

... 目前大多认为IMA是急性缺血事件和诊断ACS的有用指标,与肌钙蛋白联用对胸痛患者的诊断和处理更有价值^[2],对于鉴别心肌梗死更优于CRP^[3],总体效果可与肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)相当^[4] ...

2009

2.068

0.0

. 2009, 63(10):762-766 DOI:10.1016/j.biopha.2008.12.002

Moresco RN, da Silva DB, et al. Evaluation of ischemia-modified albumin in myocardial infarction and prostatic diseases

Abstract Background Ischemia-modified albumin (IMA) has been shown to be a rapidly rising and sensitive biochemical marker for the diagnosis of myocardial ischemia. In this study, we evaluated the levels of IMA in myocardial infarction and prostate diseases, as well as the influence of HDL cholesterol levels on C-reactive protein (CRP) and IMA levels. Methods A total of 27 patients with myocardial infarction (MI), 102 patients with benign prostatic hyperplasia (BPH), 84 patients with prostate cancer (PCA), and 21 healthy subjects were enrolled in this study. IMA levels were measured in whole studied patients. Cardiac troponin I (cTnI), cholesterol, HDL cholesterol, and CRP were measured in MI and control groups. Results IMA values were significantly higher in patients with MI (0.5215 ± 0.0241 ABSU) and BPH (0.4150 ± 0.0156 ABSU) in comparison to control subjects (0.3381 ± 0.0194 ABSU). IMA and CRP were higher in MI group, especially in patients with HDL cholesterol levels lower than 38 mg/dL. The ability of IMA to discriminate myocardial infarction was higher than CRP. Significant correlations between CRP and HDL, CRP and IMA, and HDL and IMA were reported. Conclusions IMA and CRP increase in myocardial damage, and the decrease of HDL cholesterol appears to enhance the inflammatory response. IMA also increase in benign prostate hyperplasia and this finding suggests that the diagnosis of prostate diseases must be considered on evaluation of IMA as a marker of cardiac ischemia.

2011

0.128

0.0

2008

1.704

0.0

. 2008, 26(8):874-878 DOI:10.1016/j.ajem.2007.11.023

et al . Ischemia-modified albumin levels in cerebrovascular accidents

Abstract Background Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. Methods This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. Results Mean serum IMA levels were 0.280 ± 0.045 absorbance units (ABSU) for BI patients, 0.259 ± 0.053 ABSU for ICH patients, 0.243 ± 0.061 ABSU for SAH patients, and 0.172 ± 0.045 ABSU for the control group. There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels ( P Conclusions Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.

... Gunduz 等^[5]发现脑血管疾病患者的IMA 水平较高,并可用于鉴别蛛网膜下腔出血和脑栓塞 ...

2007

2.814

0.0

... Abboud等^[6]发现在脑梗死和脑出血患者比一过性脑缺血患者发作初期IMA水平明显增高,且发病后第1个24 h内脑梗死患者IMA水平逐渐升高而脑出血患者无明显变化,认为血清IMA水平与疾病程度相关,可作为早期鉴别急性脑卒中的生化标志物 ...

2007

3.009

0.0

... IMA作为氧化应激的标志物可用来检测任何缺血事件,Falkensammer等^[7]选择健康者进行平板试验,结果显示袖带放开30min内血清IMA明显升高,30 min后恢复至基线水平 ...

2008

2.14

0.0

... Piwowar等^[8]研究发现,高血糖和氧化应激引起的慢性缺氧使糖尿病患者的IMA 升高,并且IMA与HbA_1c有明显的相关性 ...

2011

0.0

... 有研究^[9,10]发现炎症标志物MPO、CRP表达增高,且与IMA呈正相关 ...

2010

1.182

0.0

... 有研究^[9,10]发现炎症标志物MPO、CRP表达增高,且与IMA呈正相关 ...

2010

0.0

... 在糖尿病患者的研究中也发现各种氧化及炎症标志物如高敏CRP、氧化修饰低密度脂蛋白(ox-LDL)、抗-oxLDL、白细胞介素-6(IL-6)与IMA一样均升高^[11] ...

2011

1.654

0.0

. 2011, 67(3):437-441 DOI:10.1007/s13105-011-0092-4

Paraoxonase-1 and ischemia-modified albumin in patients with end-stage renal disease

1.Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke City, Tochigi 329-0498, Japan 2.Glycation, Oxidation and Disease Laboratory, Touro University—California, Vallejo, CA, USA 3.Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Yokohama, Japan

End-stage renal disease (ESRD) with and/or without treatment by hemodialysis (HD) is associated with accelerated atherosclerosis, leading to cardiovascular disease (CVD) including acute coronary syndromes. Therefore, the regulation of CVD is a crucial issue for ESRD patients. Given the recent reports that paraoxonase-1 (PON-1) and ischemia-modified albumin (IMA) could predict CVD-related mortality in ESRD, the two recent biomarkers may be useful for preventive strategies for CVD. This review paper presents current data on the relationships between PON-1, IMA, and ESRD. Many studies have shown that circulating PON-1 activity is lower in ESRD patients, and we have shown that its levels increase after HD. Although circulating IMA levels can increase before HD in ESRD patients, there remains to be little data. Our pilot study has shown a significant inverse correlation between PON-1 and IMA in ESRD patients. Although the pathogenic link between PON-1 and IMA remains speculative, considering both biomarkers may provide new insights into the prevention of CVD in ESRD patients.

... 最近研究显示在终末期肾病患者,血清IMA水平能预测心血管疾病的死亡率^[12],本研究颅脑损伤患者的损伤早期虽然与病程发展无关,但延长监测时间是否与预后有关,或是与死亡率有关,还值得进一步的调查 ...