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重度酒精滥用受试者的血清蛋白质组学图谱

Serum Proteomic Profiles In Subjects with Heavy Alcohol Abuse.

作者信息

Liangpunsakul Suthat, Lai Xianyin, Ringham Heather N, Crabb David W, Witzmann Frank A

机构信息

Division of Gastroenterology/Hepatology, Clarian/IU Digestive Diseases Center, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202.

出版信息

J Proteomics Bioinform. 2009 May 20;2:236-243. doi: 10.4172/jpb.1000082.

Abstract

OBJECTIVES

The abuse of alcohol is a major public health problem, and the diagnosis and care of patients with alcohol abuse and dependence is hindered by the lack of tests that can detect dangerous levels of drinking or relapse during therapy. Gastroenterologists and other healthcare providers find it very challenging to obtain an accurate alcohol drinking history. We hypothesized that the effects of ethanol on numerous systems may well be reflected in changes in quantity or qualities of constituent or novel plasma proteins or protein fragments. Organ/tissue-specific proteins may be released into the blood stream when cells are injured by alcohol, or when systemic changes are induced by alcohol, and such proteins would be detected using a proteomic approach. The objective of this pilot study was to determine if there are plasma proteome profiles that correlate with heavy alcohol use. METHODS: Paired serum samples, before and after intensive alcohol treatment, were obtained from subjects who attended an outpatient alcohol treatment program. Serum proteomic profiles using MALDI -OTOF Mass Spectrometry were compared between pre- and post treatment samples. RESULTS: Of 16 subjects who enrolled in the study, 8 were females. The mean age of the study subjects was 49 yrs. The baseline laboratory data showed elevated AST (54 ± 37 IU/L), ALT (37 ± 19 IU/L), and MCV (99 ± 5 fl). Self-reported pre-treatment drinking levels for these subjects averaged 17 ± 7drinks/day and 103 ± 37 drinks/week. Mass spectrometry analyses showed a novel 5.9 kDa protein, a fragment of alpha fibrinogen, isoform 1, that might be might be a new novel marker for abusive alcohol drinking. CONCLUSIONS: We have shown in this pilot study that several potential protein markers have appeared in mass spectral profiles and that they may be useful clinically to determine the status of alcohol drinking by MALDI -OTOF mass spectrometry, especially a fragment of alpha fibrinogen, isoform 1. However, a large-scale study is needed to confirm and validate our current results.

摘要

目的

酒精滥用是一个重大的公共卫生问题,而酒精滥用和依赖患者的诊断与护理因缺乏能够检测危险饮酒水平或治疗期间复发情况的检测方法而受到阻碍。胃肠病学家和其他医疗服务提供者发现获取准确的饮酒史极具挑战性。我们推测乙醇对众多系统的影响很可能反映在血浆中组成蛋白或新蛋白或蛋白片段的数量或质量变化上。当细胞受到酒精损伤或酒精引起全身变化时,器官/组织特异性蛋白可能会释放到血流中,并且可以使用蛋白质组学方法检测此类蛋白。这项初步研究的目的是确定是否存在与大量饮酒相关的血浆蛋白质组图谱。方法:从参加门诊酒精治疗项目的受试者中获取强化酒精治疗前后的配对血清样本。使用基质辅助激光解吸电离飞行时间质谱法比较治疗前和治疗后样本的血清蛋白质组图谱。结果:参与该研究的16名受试者中,8名是女性。研究对象的平均年龄为49岁。基线实验室数据显示谷草转氨酶(AST,54±37 IU/L)、谷丙转氨酶(ALT,37±19 IU/L)和平均红细胞体积(MCV,99±5 fl)升高。这些受试者自我报告的治疗前饮酒水平平均为每天17±7杯,每周103±37杯。质谱分析显示一种新的5.9 kDa蛋白,即α纤维蛋白原1亚型的一个片段,可能是酒精滥用的一个新的标记物。结论:我们在这项初步研究中表明,质谱图谱中出现了几种潜在的蛋白质标记物,它们可能在临床上有助于通过基质辅助激光解吸电离飞行时间质谱法确定饮酒状态,尤其是α纤维蛋白原1亚型的一个片段。然而,需要进行大规模研究来证实和验证我们目前的结果。

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