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酒精性肝病患者全血内毒素结合能力降低。

Decreased endotoxin-binding capacity of whole blood in patients with alcoholic liver disease.

作者信息

Schäfer C, Greiner B, Landig J, Feil E, Schütz E T, Bode J C, Bode C

机构信息

Department of Internal Medicine, Hohenheim University, Stuttgart, Germany.

出版信息

J Hepatol. 1997 Mar;26(3):567-73. doi: 10.1016/s0168-8278(97)80422-9.

DOI:10.1016/s0168-8278(97)80422-9
PMID:9075664
Abstract

BACKGROUND/AIMS: The proinflammatory effects of endotoxemia, which is often observed in alcohol-abusing patients with various degrees of liver disease, may be modulated by changes in the concentration of endotoxin binding factors. Therefore, the plasma endotoxin concentration and the overall endotoxin binding capacity of whole blood were measured in these patients.

METHODS

Patients with minor (A1; n=27), more pronounced (A2; n=13), cirrhotic alcoholic liver disease (A3; n=18), and non-alcoholic cirrhosis (NC; n=6), and 15 healthy control persons (HC) were included in the study. Endotoxin plasma levels were determined using a standardized limulus assay. A modified assay was applied to additionally detect tightly bound endotoxin. To measure the endotoxin-binding capacity, aliquots of whole blood were incubated with serial dilutions of endotoxin, supernatants were obtained, and endotoxin retrieval was estimated by addition of limulus lysate, followed by photometric measurement of the maximal reaction velocity (dODmax). Endotoxin binding capacity equals the endotoxin concentration at which dODmax reaches a predefined threshold.

RESULTS

All groups of alcohol abusers had significantly elevated endotoxin plasma levels with a considerable portion of 'bound' endotoxin. Conversely, the endotoxin binding capacity was markedly diminished, mainly in patients with more advanced liver disease (A1: 85.8% of the control value [non-significant vs. controls]; A2: 25.4% [p<0.05]; A3: 43.6% [p<0.02], NC: 43.2%).

CONCLUSIONS

The endotoxin-binding capacity is diminished in patients with alcoholic and non-alcoholic cirrhosis, as well as in less advanced alcoholic liver disease. Reduced endotoxin binding may contribute to the adverse effects of endotoxemia.

摘要

背景/目的:内毒素血症的促炎作用在患有不同程度肝病的酗酒患者中经常可见,其可能会受到内毒素结合因子浓度变化的调节。因此,对这些患者的血浆内毒素浓度和全血的总内毒素结合能力进行了测量。

方法

本研究纳入了患有轻度(A1组;n = 27)、更严重(A2组;n = 13)、肝硬化酒精性肝病(A3组;n = 18)以及非酒精性肝硬化(NC组;n = 6)的患者,以及15名健康对照者(HC组)。使用标准化鲎试剂法测定血浆内毒素水平。采用改良检测法额外检测紧密结合的内毒素。为测量内毒素结合能力,将全血 aliquots 与内毒素系列稀释液孵育,获取上清液,加入鲎试剂裂解物后估计内毒素回收量,随后通过光度法测量最大反应速度(dODmax)。内毒素结合能力等于 dODmax 达到预定义阈值时的内毒素浓度。

结果

所有酗酒组患者的血浆内毒素水平均显著升高,且有相当一部分“结合”内毒素。相反,内毒素结合能力明显降低,主要见于肝病更严重的患者(A1组:为对照值的85.8%[与对照组无显著差异];A2组:25.4%[p<0.05];A3组:43.6%[p<0.02],NC组:43.2%)。

结论

酒精性和非酒精性肝硬化患者以及病情较轻的酒精性肝病患者的内毒素结合能力降低。内毒素结合减少可能导致内毒素血症的不良反应。

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