Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr

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• 作者：Kazuya Kitamori (1) (2)
  Hisao Naito (1)
  Hazuki Tamada (1) (2)
  Miya Kobayashi (2)
  Daisuke Miyazawa (2)
  Yuko Yasui (2)
  Kunihiro Sonoda (2)
  Satoru Tsuchikura (3)
  Naomi Yasui (4)
  Katsumi Ikeda (4)
  Takashi Moriya (1)
  Yukio Yamori (5)
  Tamie Nakajima (1)
  
• 关键词：SHRSP5/Dmcr ; High ; fat and high ; cholesterol ; containing diet ; Non ; alcoholic fatty liver disease ; Non ; alcoholic steatohepatitis ; Fibrosis
• 刊名：Environmental Health and Preventive Medicine
• 出版年：2012
• 出版时间：May 2012
• 年：2012
• 卷：17
• 期：3
• 页码：173-182
• 全文大小：986KB
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• 作者单位：Kazuya Kitamori (1) (2)
  Hisao Naito (1)
  Hazuki Tamada (1) (2)
  Miya Kobayashi (2)
  Daisuke Miyazawa (2)
  Yuko Yasui (2)
  Kunihiro Sonoda (2)
  Satoru Tsuchikura (3)
  Naomi Yasui (4)
  Katsumi Ikeda (4)
  Takashi Moriya (1)
  Yukio Yamori (5)
  Tamie Nakajima (1)
  
  1. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
  2. College of Human Life and Environment, Kinjo Gakuin University, Nagoya, Japan
  3. Disease Model Cooperative Research Association, Kyoto, Japan
  4. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, Nishinomiya, Japan
  5. Institute for World Health Development, Mukogawa Women’s University, Nishinomiya, Japan
  

文摘

Objectives Patients with nonalcoholic fatty liver disease are increasing worldwide, and preventive measures are an urgent need and primary concern today. Aim This study aimed to develop and clarify the usefulness of the SHRSP5/Dmcr rat, derived from a stroke-prone spontaneously hypertensive rat, as a novel animal model for time-course analysis of steatohepatitis and the severe fibrosis progression often observed in the disease. Methods Ten-week-old male SHRSP5/Dmcr rats were divided into six groups: half were fed a high-fat and high-cholesterol-containing diet (HFC diet), and the others the control, stroke-prone (SP) diet for 2, 8, and 14?weeks. Results The HFC diet significantly increased serum transaminase and gamma glutamyl transpeptidase activities, tumor necrosis factor alpha levels, and serum and hepatic total cholesterol levels over time. In contrast, this diet decreased serum albumin, glucose, and adiponectin levels throughout or the later stage of the feeding period, but did not influence serum insulin levels. Histopathologically, the HFC diet increased microvesicular steatosis, and focal or spotty necrosis with lymphocyte infiltrations were observed in the liver at 2?weeks, macrovesicular steatosis, ballooned hepatocytes with Mallory-Denk body formation in some, and multilobular necrosis and fibrosis at 8?weeks. Interestingly, this fibrosis formed a honeycomb network at 14?weeks. These changes are very similar to those observed in patients with non-alcoholic steatohepatitis. Conclusions SHRSP5/Dmcr rats appear to be a useful model for analyzing the time-dependent changes of HFC diet-induced steatohepatitis and fibrosis progression.