Miyaoka Yuta, Jin Denan, Tashiro Keitaro, Masubuchi Shinsuke, Ozeki Maiko, Hirokawa Fumitoshi, Hayashi Michihiro, Takai Shinji, Uchiyama Kazuhisa
Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan.
Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan.
Exp Anim. 2018 May 10;67(2):239-247. doi: 10.1538/expanim.17-0126. Epub 2018 Jan 1.
Nonalcoholic steatohepatitis (NASH), in which there is steatosis and fibrosis in the liver, is linked to metabolic syndrome and progresses to hepatic cirrhosis. In this study, a novel hamster NASH model derived from metabolic syndrome was made using hamsters. Hamsters were fed a normal or a high-fat and high-cholesterol (HFC) diet for 12 weeks. Body weight and the ratio of liver weight to body weight were significantly greater in HFC diet-fed hamsters than in normal diet-fed hamsters. Triglyceride, low-density lipoprotein cholesterol, and glucose levels in blood were significantly increased in HFC diet-fed hamsters, and blood pressure also tended to be high, suggesting that the HFC diet-fed hamsters developed metabolic syndrome. Hepatic steatosis and fibrosis were observed in liver sections of HFC diet-fed hamsters, as in patients with NASH, but they were not seen in normal diet-fed hamsters. Chymase generates angiotensin II and transforming growth factor (TGF)-β, both of which are related to hepatic steatosis and fibrosis, and a significant augmentation of chymase activity was observed in livers from HFC diet-fed hamsters. Both angiotensin II and TGF-β were also significantly increased in livers of HFC diet-fed hamsters. Thus, HFC diet-fed hamsters might develop metabolic syndrome-derived NASH that clinically resembles that in NASH patients.
非酒精性脂肪性肝炎（NASH），即肝脏出现脂肪变性和纤维化，与代谢综合征相关，并会发展为肝硬化。在本研究中，利用仓鼠构建了一种源自代谢综合征的新型仓鼠NASH模型。将仓鼠分别喂食正常饮食或高脂高胆固醇（HFC）饮食12周。喂食HFC饮食的仓鼠的体重以及肝脏重量与体重之比显著高于喂食正常饮食的仓鼠。喂食HFC饮食的仓鼠血液中的甘油三酯、低密度脂蛋白胆固醇和葡萄糖水平显著升高，血压也有升高趋势，这表明喂食HFC饮食的仓鼠患上了代谢综合征。在喂食HFC饮食的仓鼠的肝脏切片中观察到了肝脂肪变性和纤维化，与NASH患者的情况一样，但在喂食正常饮食的仓鼠中未观察到。糜酶可生成血管紧张素II和转化生长因子（TGF）-β，二者均与肝脂肪变性和纤维化有关，在喂食HFC饮食的仓鼠的肝脏中观察到糜酶活性显著增强。血管紧张素II和TGF-β在喂食HFC饮食的仓鼠的肝脏中也显著增加。因此，喂食HFC饮食的仓鼠可能会患上源自代谢综合征的NASH，其临床表现与NASH患者相似。
