Thiel Karolin, Schenk Martin, Sipos Bence, Sperveslage Jan, Peter Andreas, Morgalla Matthias H, Grasshoff Christian, Königsrainer Alfred, Thiel Christian
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.
Hepatol Int. 2014 Jan;8(1):128-36. doi: 10.1007/s12072-013-9491-7. Epub 2013 Dec 4.
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.
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.
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).
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.
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。
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。
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)。
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。