Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality
Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality
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DOI：
10.1016/s0168-8278(02)00011-9
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发表时间：
2002-04-01
影响因子：
25.7
通讯作者：
Alexander, B
中科院分区：
文献类型：
--
作者：
Li, XN;Benjamin, IS;Alexander, B
背景/目的：肝毒素诱导的大鼠肝硬化模型受到肝硬化广泛异质性的限制。本研究开发了一种改良的，可靠的，可重复的技术，通过它的肝脏和全身反应硫代乙酰胺诱导肝硬化监测每周的重量changes.Methods：雄性Wistar大鼠（200-230 g）被分为三组。第1组（n = 20）连续12周饮用含0.03%（w/v）硫代乙酰胺的饮用水。第2组（它= 20）接受与初始浓度相同浓度的0.03%硫代乙酰胺，该初始浓度根据肝硬化诱导期间对硫代乙酰胺响应的每周体重变化进行修改。结果：第1组死亡率为30%，肝硬化发生率为45%。相反，在第2组中没有死亡，并且在90%的大鼠中发现了发育良好的大结节性肝硬化，其与显著的门静脉高压相关，如门静脉压力增加所示（13.6 +/- 0.4 vs. 9.1 +/- 0.3 mmHg，舒张期vs.对照，P < 0.01，Student非配对t检验）。对硫代乙酰胺的反应变化可以通过每周体重变化容易地监测，以将死亡率降低至零，同时增加大鼠中诱导的肝硬化的产生和质量。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版，版权所有。
Background/Aims: Hepatotoxin-induced rat models of liver cirrhosis are limited by the wide heterogeneity of cirrhosis produced. The present study developed a modified, reliable, and reproducible technique by which hepatic and systemic responses to thioacetamide during induction of cirrhosis were monitored by weekly weight changes.Methods: Male Wistar rats (200-230 g) were divided into three groups. Group 1 (n = 20) received continuous administration of 0.03% (w/v) thioacetamide in the drinking water for 12 weeks. Group 2 (it = 20) received the same concentration of 0.03% thioacetamide as an initial concentration that was modified according to weekly weight changes in response to thioacetamide during the induction of cirrhosis. Group 3 (it = 6) received normal water and served as controls.Results: Mortality of Group 1 was 30% and the production of cirrhosis was only 45%. In contrast, there were no deaths in Group 2 and well-developed macronodular cirrhosis was found in 90% of the rats which was associated with significant portal hypertension, as indicated by increased portal venous pressure (13.6 +/- 0.4 vs. 9.1 +/- 0.3 mmHg, cirrhotic vs. control, respectively, P < 0.01, Student's unpaired t-test).Conclusions: Variations in responses to thioacetamide can be easily monitored by weekly weight changes to reduce mortality to zero and simultaneously increase the production and quality of cirrhosis induced in rats. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.