High-fat emulsion-induced rat model of nonalcoholic steatohepatitis
High-fat emulsion-induced rat model of nonalcoholic steatohepatitis
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DOI：
10.1016/j.lfs.2006.03.021
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发表时间：
2006-08-08
期刊：
影响因子：
6.1
通讯作者：
Wang, Yuanyuan
中科院分区：
文献类型：
--
作者：
Zou, Yuhong;Li, Jun;Wang, Yuanyuan
非酒精性脂肪肝（NAFLD）正在成为一种常见的医学问题。非酒精性脂肪性肝炎（NASH）是NAFLD进展到更晚期阶段（如肝纤维化、肝硬化甚至肝细胞癌）的关键转折点。然而，由于缺乏合适的实验模型，NASH致病或治疗因素的研究受到阻碍。本研究旨在建立高脂乳剂诱导的NASH大鼠模型。雄性Sprague-Dawley大鼠通过管饲法喂食高脂肪乳剂6周。检查动物的体重增加、血清和肝脏生化、胰岛素敏感性、肝脏丙二醛（MDA）、超氧化物歧化酶（SOD）和组织形态，以及肝脏中细胞色素P-450 2 E1（CYP 2 E1）和过氧化物酶体增殖物激活受体α（PPAR α）的表达。结果表明，高脂乳剂组大鼠出现肥胖、转氨酶活性异常、高脂血症、高胰岛素血症、高血糖和胰岛素抵抗。模型组大鼠血清TNF-α、总胆固醇（TC）、甘油三酯（TG）、丙二醛（MDA）水平升高，肝脏SOD水平降低。免疫印迹分析显示，NASH模型大鼠肝脏中CYP 2 E1的表达增加，而PPAR α的表达减少。此外，形态学评价显示，肝脏脂肪变性，炎症和线粒体病变也在该模型中重现。结论：高脂乳剂灌胃法可建立一种实用、可重复的大鼠脂肪性肝炎模型。该模型提供了一种有价值的研究工具，并再现了人类NASH的许多临床指标。(c)2006年爱思唯尔公司All rights reserved.
Non-alcoholic fatty liver disease (NAFLD) is emerging as a common medical problem. Nonalcoholic steatohepatitis (NASH) is the critical turning point at which NAFLD progresses to more advanced stages such as hepatic fibrosis, cirrhosis and even hepatocellular carcinoma. However, the study of the pathogenic or therapeutic factors involved in NASH has been hampered by the absence of a suitable experimental model. The aim of the present work was to establish a high-fat emulsion-induced rat model of NASH. Male Sprague-Dawley rats were fed a high-fat emulsion via gavage for 6 weeks. Animals were examined for weight gain, serum and hepatic biochemistry, insulin sensitivity, hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and tissue morphology, as well as cytochrome P-450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor alpha (PPAR alpha) expression in the liver. The results showed that rats treated with high-fat emulsion became obese, demonstrated abnormal aminotransferase activity, hyperlipoidemia, hyperinsulinemia, hyperglycemia and insulin resistance. The model rats exhibited an increased concentration of serum TNF-alpha, total cholesterol (TC), triglyceride (TG), MDA and reduced SOD levels in the liver. Immunoblot analysis showed that the expression of CYP2E1 was increased, whereas PPAR alpha was reduced in the NASH model rat liver. Moreover, morphological evaluation revealed that hepatic steatosis, inflammation and mitochondrial lesions were also reproduced in this model. In conclusion, a practical and repeatable new rat model of steatohepatitis was established by feeding with high-fat emulsion via gavage. This model provides a valuable research tool and reproduces many of the clinical indices of human NASH. (c) 2006 Elsevier Inc. All rights reserved.