Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr
| Autor: | Yuko Yasui, Katsumi Ikeda, Yukio Yamori, Takashi Moriya, Naomi Yasui, Miya Kobayashi, Kunihiro Sonoda, Tamie Nakajima, Satoru Tsuchikura, Hisao Naito, Kazuya Kitamori, Daisuke Miyazawa, Hazuki Tamada |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Liver Cirrhosis Male medicine.medical_specialty Necrosis Microvesicular Steatosis Blood Pressure Diet High-Fat Weight Gain Cholesterol Dietary chemistry.chemical_compound Spontaneously hypertensive rat Fibrosis Albumins Rats Inbred SHR Internal medicine Nonalcoholic fatty liver disease medicine Animals Insulin Transaminases Adiponectin Tumor Necrosis Factor-alpha business.industry Cholesterol Public Health Environmental and Occupational Health Regular Article gamma-Glutamyltransferase General Medicine medicine.disease Rats Fatty Liver Disease Models Animal Endocrinology Liver chemistry Disease Progression medicine.symptom Steatohepatitis business Biomarkers |
| Zdroj: | Environmental Health and Preventive Medicine. 17:173-182 |
| ISSN: | 1347-4715 1342-078X |
| DOI: | 10.1007/s12199-011-0235-9 |
| Popis: | Patients with nonalcoholic fatty liver disease are increasing worldwide, and preventive measures are an urgent need and primary concern today. 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. 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. 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. SHRSP5/Dmcr rats appear to be a useful model for analyzing the time-dependent changes of HFC diet-induced steatohepatitis and fibrosis progression. |
| Databáze: | OpenAIRE |
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