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二甲基亚硝胺诱导犬肝毒性作为进行性犬肝病模型

Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease.

作者信息

Boothe D M, Jenkins W L, Green R A, Corrier D E, Cullen J M, Boothe H W, Weise D

机构信息

Department of Veterinary Physiology and Pharmacology, Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station 77843-4466.

出版信息

Am J Vet Res. 1992 Mar;53(3):411-20.

PMID:1595969
Abstract

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.

摘要

本文描述了在比格犬中建立的毒素诱导的进行性肝炎模型。将毒素二甲基亚硝胺经口给予18只比格犬;6只犬作为对照组。随着疾病进展,监测临床症状和实验室检查结果,并用于确定疾病的终点。安乐死后,对组织学病变进行评分,并用于得出每只犬的总严重程度评分。然后,根据严重程度评分将18只犬分为轻度、中度或重度3组肝病。按时间顺序描述了所有犬的临床实验室检查结果的变化,包括肝功能检查,以及提示肝病的临床症状。比较了临床实验室检查结果的组均值和可量化的临床症状(如体重减轻和腹水积聚)。与其他犬肝病实验模型相比,该模型具有几个优点。这些优点包括肝脏特异性、与自然疾病的相似性(如多发性肝外门体分流的发生),以及将疾病滴定至所需终点的能力。该模型的主要缺点是该药物对人类具有毒性,且个体动物对毒素的反应存在差异,这使得无法预先将动物分组。

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