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鹅膏毒素中毒后的急性肝衰竭:一种用于检测肝脏再生预后标志物的猪模型

Acute liver failure after amanitin poisoning: a porcine model to detect prognostic markers for liver regeneration.

作者信息

Thiel Karolin, Schenk Martin, Sipos Bence, Sperveslage Jan, Peter Andreas, Morgalla Matthias H, Grasshoff Christian, Königsrainer Alfred, Thiel Christian

机构信息

Department of General, Visceral and Transplant Surgery, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.

Institute of General Pathology and Neuropathology, University Hospital, Liebermeisterstrasse 8, 72076, Tübingen, Germany.

出版信息

Hepatol Int. 2014 Jan;8(1):128-36. doi: 10.1007/s12072-013-9491-7. Epub 2013 Dec 4.

Abstract

PURPOSE

Over 90 % of fatal mushroom poisoning occurs after ingestion of amanitin-containing species. This study aimed to investigate markers indicating spontaneous liver regeneration in a porcine acute liver failure (ALF) model after α-amanitin intoxication.

METHODS

German landrace pigs received either 0.15 mg/kg (n = 5) α-amanitin intravenously or 0.35 mg/kg (n = 5) intraportally. Pigs were invasively monitored and kept under general anesthesia throughout the experiment. Laboratory parameters were analyzed every 8 h.

RESULTS

ALF occurred in all animals (10/10) 41 ± 3 h after intoxication. All pigs receiving 0.35 mg/kg α-amanitin and one pig receiving 0.15 mg/kg α-amanitin died 57 ± 16 h after the primary onset of ALF. Four pigs of the 0.15 mg/kg intoxication group recovered spontaneously from ALF after 56 ± 6 h. Starting at 32 h after intoxication, significantly higher values of albumin and total plasma protein could be measured in surviving animals (p < 0.05). A significant temporary increase in the tumor necrosis factor alpha (TNF-α) plasma concentration was detected 40-80 h after intoxication in recovering animals (p < 0.05).

CONCLUSIONS

This porcine model represents a novel tool to analyse multiple aspects of liver regeneration following α-amanitin poisoning to allow early discrimination between a fatal course and survivors. Decreased albumin and total plasma protein concentrations in the early intoxication phase indicated a lethal outcome, while an increase in the TNF-α plasma concentration was identified as the earliest prognostic plasma marker detecting liver regeneration a long time before liver function was biochemically and clinically impaired.

摘要

目的

超过90%的致命蘑菇中毒发生在摄入含鹅膏毒素的物种之后。本研究旨在调查在α-鹅膏毒素中毒后的猪急性肝衰竭(ALF)模型中指示自发性肝再生的标志物。

方法

德国长白猪静脉注射0.15mg/kg(n = 5)α-鹅膏毒素或经门静脉注射0.35mg/kg(n = 5)α-鹅膏毒素。在整个实验过程中对猪进行侵入性监测并使其处于全身麻醉状态。每8小时分析一次实验室参数。

结果

中毒后41±3小时,所有动物(10/10)均发生急性肝衰竭。所有接受0.35mg/kgα-鹅膏毒素的猪和一只接受0.15mg/kgα-鹅膏毒素的猪在急性肝衰竭初次发作后57±16小时死亡。0.15mg/kg中毒组的四只猪在56±6小时后从急性肝衰竭中自发恢复。中毒后32小时起,存活动物的白蛋白和总血浆蛋白值显著升高(p < 0.05)。在恢复中的动物中毒后40 - 80小时检测到肿瘤坏死因子α(TNF-α)血浆浓度显著暂时升高(p < 0.05)。

结论

该猪模型是一种新型工具,可用于分析α-鹅膏毒素中毒后肝再生的多个方面,以便在致命病程和幸存者之间进行早期区分。中毒早期白蛋白和总血浆蛋白浓度降低表明预后不良,而TNF-α血浆浓度升高被确定为最早的预后血浆标志物,早在肝功能出现生化和临床损害之前就能检测到肝再生。

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