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

Kazuya Kitamori, Hisao Naito, Hazuki Tamada, Miya Kobayashi, Daisuke Miyazawa, Yuko Yasui, Kunihiro Sonoda, Satoru Tsuchikura, Naomi Yasui, Katsumi Ikeda, Takashi Moriya, Yukio Yamori, Tamie Nakajima

研究成果: Article査読

36 被引用数 (Scopus)

抄録

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 highcholesterol- 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.

本文言語English
ページ(範囲)173-182
ページ数10
ジャーナルEnvironmental Health and Preventive Medicine
17
3
DOI
出版ステータスPublished - 05-2012

All Science Journal Classification (ASJC) codes

  • 公衆衛生学、環境および労働衛生

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