A diet-induced Sprague-Dawley rat model of nonalcoholic steatohepatitis-related cirrhosis

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• 作者：Mayuko Ichimura^a ; ^b ; Miki Masuzumi^c ; Miku Kawase^c ; Mika Sakaki^c ; Shizuka Tamaru^a ; ^c ; Yasuo Nagata^a ; Kazunari Tanaka^a ; ^c ; Kazuhito Suruga^a ; ^c ; Koichi Tsuneyama^d ; Satoru Matsuda^b ; Katsuhisa Omagari^a ; ^c ; ^{omagari@sun.ac.jp}
• 关键词：Liver cirrhosis ; Nonalcoholic steatohepatitis ; High-fat and high-cholesterol ; Cholic acid ; Animal model
• 刊名：The Journal of Nutritional Biochemistry
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：40
• 期：Complete
• 页码：62-69
• 全文大小：1199 K
• 卷排序：40

文摘

Certain modified diets containing saturated fatty acids, cholesterol or fructose lead to the development of nonalcoholic steatohepatitis (NASH)-related fibrosis in rodents; however, progression to cirrhosis is rare. Experimental liver cirrhosis models have relied on genetic manipulation or administration of hepatotoxins. This study aimed to establish a reliable dietary model of NASH-related cirrhosis in a relatively short period. Male Sprague–Dawley rats (9 weeks of age) were randomly assigned to normal, high-fat (HF), or two types (1.25% or 2.5% cholesterol) of high-fat and high-cholesterol (HFC) diets for 18 weeks. All HFC diets contained 2% cholic acid by weight. Histopathological analysis revealed that the HFC diets induced obvious hepatic steatosis, inflammation with hepatocyte ballooning and advanced fibrosis (stage 3–4) in all 12 rats at 27 weeks of age. In contrast, all five rats given the HF diet developed mild steatosis and inflammation without fibrosis. The amount of cholesterol in the liver and hepatocellular mitochondrial and microsomal fractions was significantly higher in rats fed the HFC diets than the normal or HF diets. The HFC diets significantly suppressed mRNA levels of microsomal triglyceride transfer protein, adenosine triphosphate binding cassette transporter G5, bile acid CoA: amino acid N-acyltransferase and bile salt export pump, as well as the enzymatic activity of carnitine palmitoyltransferase in the liver. In conclusion, the HFC diets induced liver cirrhosis in conjunction with hepatic features of NASH in Sprague–Dawley rats within 18 weeks, and altered gene expression and enzyme activity to accumulate lipid and bile acid in the liver.