Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis
Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis
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DOI：
10.1007/s00535-006-1883-1
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发表时间：
2006-10-01
影响因子：
6.3
通讯作者：
Shimada, Yutaka
中科院分区：
文献类型：
--
作者：
Kainuma, Mosaburo;Fujimoto, Makoto;Shimada, Yutaka
背景患有代谢综合征的患者数量正在迅速增加。代谢综合征引起包括肝脏在内的多种器官的严重病理变化，其主要表型为非酒精性脂肪性肝病（NAFLD）。NAFLD具有从简单的脂肪改变到具有显著纤维化的严重脂肪性肝炎的广泛谱。最近，已经提出了几种NAFLD的实验动物模型。然而，大多数是通过相当人为的条件建立的，如遗传改变。在本研究中，我们试图建立一个独特的动物模型，模仿一些生理病理学特征的NAFLD使用高胆固醇喂养的兔子。方法.将喂食含1%胆固醇的标准兔饲料8周和12周的雄性兔与对照组（6只兔/组）进行比较。食物的重量严格限制在每天100摄氏度/只兔子。结果各组间体重和空腹血浆胰岛素水平无显著差异。相比之下，特征性细纤维化从小静脉周围延伸到细胞周围区域，并且在胆固醇喂养的兔的肝脏中的小静脉周围区域中观察到微泡脂肪改变伴气球样变性。血清胆固醇水平升高、肝星状细胞活化和暴露于氧化应激也被确认。结论.胆固醇喂养的兔子具有NAFLD的几个生理病理学特征。由于该模型未显示胰岛素抵抗或肥胖，因此可能有助于阐明主要与高脂血症相关的NAFLD机制。
Background. The number of patients suffering from metabolic syndrome is increasing rapidly. Metabolic syndrome causes severe pathological changes in various organs, including the liver, and its main phenotype is nonalcoholic fatty liver disease (NAFLD). NAFLD has a broad spectrum ranging from simple fatty change to severe steatohepatitis with marked fibrosis. Recently, several experimental animal models for NAFLD have been proposed. However, most were established by rather artificial conditions such as genetic alteration. In the present study, we tried to establish a unique animal model mimicking some of the physiopathological features of NAFLD using high-cholesterol-fed rabbits. Methods. Male rabbits fed with standard rabbit food containing 1% cholesterol for 8 weeks and 12 weeks were compared to controls (six rabbits/group). The weight of food was strictly restricted to 100 degrees Ceg/rabbit per day. Results. Body weights and fasting plasma insulin levels showed no significant differences among the groups. In contrast, characteristic fine fibrosis was extended from perivenular to pericellular areas, and microvesicular fatty change with ballooning degeneration was observed in perivenular areas in livers of the cholesterol-fed rabbits. Increase of serum cholesterol level, activation of hepatic stellate cells, and exposure to oxidative stress were also recognized. Conclusions. Cholesterol-fed rabbits share several physiopathological features of NAFLD. Because this model did not show insulin resistance or obesity, it may be useful for elucidating the mechanism of NAFLD related mainly to hyperlipidemia.