Rodent nutritional model of non-alcoholic steatohepatitis: Species, strain and sex difference studies
Rodent nutritional model of non-alcoholic steatohepatitis: Species, strain and sex difference studies
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DOI：
10.1046/j.1440-1746.2003.03198.x
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发表时间：
2003-11-01
影响因子：
4.1
通讯作者：
Hall, PD
中科院分区：
文献类型：
--
作者：
Kirsch, R;Clarkson, V;Hall, PD
背景和目的：蛋氨酸胆碱缺乏（MCD）饮食导致啮齿动物脂肪性肝炎。本研究的目的是调查种属，品系和性别差异，在这种营养模型的非酒精性脂肪性肝炎（NASH.Methods）：雄性和雌性Wistar，Long-Evans和Sprague-Dawley大鼠，和C57/BL 6小鼠（n = 6每组）喂食MCD饲料4周。对照组接受相同的饮食，补充胆碱酒石酸氢盐（0.2% w/w）和蛋氨酸（0.3% w/w）。肝脏病理（脂肪变性和炎症）和超微结构，肝脏脂质谱比较各组间的血脂（总脂质、甘油三酯、脂质过氧化产物）、肝体质量比和血清丙氨酸氨基转移酶（ALT）水平。喂食MCD饲料的雄性大鼠发生了更严重的脂肪变性与雌性大鼠相比，雌性大鼠肝脏脂质含量显著升高（P <0.001），血清ALT水平显著升高（P < 0.005）。与Long-Evans和Sprague-Dawley大鼠相比，Wistar大鼠（两种性别）具有更高的肝脏脂质水平（P <0.05）、血清ALT水平（P < 0.05）和肝脏质量/体重比（P < 0.025）。雌性Wistar大鼠的脂肪变性明显大于其它两种品系（P < 0.05）。喂食MCD饲料的所有大鼠均发生肝脂肪变性，但坏死和炎症是次要特征，不存在纤维化。与Wistar大鼠相比，雄性C57/BL 6小鼠的炎性病灶明显增加脂质过氧化终产物（P < 0.001）（游离硫代巴比妥酸反应物质）（P < 0.005），线粒体损伤，而脂肪变性较少（P < 0.005），降低肝脏甘油三酯水平，（P < 0.005）和降低早期脂质过氧化产物（共轭二烯和脂质氢过氧化物;分别为P < 0.005和P < 0.01）。结论：Wistar品系和雄性与MCD饲料大鼠中最大程度的脂肪变性相关。在所研究的组中，雄性C57/BL 6小鼠发生最多的炎症和坏死、脂质过氧化和超微结构损伤，并且最接近NASH的组织学特征。(C)2003年Blackwell Publishing Asia Pty Ltd.
Background and Aim: The methionine choline-deficient (MCD) diet leads to steatohepatitis in rodents. The aim of the present study was to investigate species, strain and sex differences in this nutritional model of non-alcoholic steatohepatitis (NASH).Methods: Male and female Wistar, Long-Evans and Sprague-Dawley rats, and C57/BL6 mice (n = 6 per group) were fed a MCD diet for 4 weeks. Control groups received an identical diet supplemented with choline bitartrate (0.2% w/w) and methionine (0.3% w/w). Liver pathology (steatosis and inflammation) and ultrastructure, liver lipid profile (total lipids, triglycerides, lipid peroxidation products), liver : body mass ratios and serum alanine aminotransferase (ALT) levels were compared between these groups.Results: The MCD diet-fed male rats developed greater steatosis (P < 0.001), had higher liver lipid content (P < 0.05) and had higher serum ALT levels (P < 0.005) than did female rats. Wistar rats (both sexes) had higher liver lipid levels (P < 0.05), serum ALT levels (P < 0.05), and liver mass : body mass ratios (P < 0.025) than did Long-Evans and Sprague-Dawley rats. In female groups, Wistar rats showed greater fatty change than did the other two strains (P < 0.05). All rats fed the MCD diet developed hepatic steatosis, but necrosis and inflammation were minor features and fibrosis was absent. Compared with Wistar rats, male C57/ BL6 mice showed a marked increase in inflammatory foci (P < 0.001), end products of lipid peroxidation (free thiobarbituric acid reactive substances) (P < 0.005), and mitochondrial injury, while showing less steatosis (P < 0.005), lower hepatic triglyceride levels, (P < 0.005) and lower early lipid peroxidation products (conjugated dienes and lipid hydroperoxides; P < 0.005 and P < 0.01, respectively).Conclusions: The Wistar strain and the male sex are associated with the greatest degree of steatosis in rats subjected to the MCD diet. Of the groups studied, male C57/ BL6 mice develop the most inflammation and necrosis, lipid peroxidation, and ultrastructural injury, and best approximate the histological features of NASH. (C) 2003 Blackwell Publishing Asia Pty Ltd.