RRC ID 27756
著者 Kitamori K, Naito H, Tamada H, Kobayashi M, Miyazawa D, Yasui Y, Sonoda K, Tsuchikura S, Yasui N, Ikeda K, Moriya T, Yamori Y, Nakajima T.
タイトル Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr.
ジャーナル Environ Health Prev Med
Abstract 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.
巻・号 17(3)
ページ 173-82
公開日 2012-5-1
DOI 10.1007/s12199-011-0235-9
PMID 21853259
PMC PMC3348249
MeSH Adiponectin / blood Albumins / metabolism Animals Biomarkers / blood Blood Glucose / metabolism Blood Pressure Cholesterol / blood Cholesterol, Dietary / adverse effects* Diet, High-Fat / adverse effects* Disease Models, Animal* Disease Progression Fatty Liver / blood Fatty Liver / etiology* Fatty Liver / pathology Insulin / blood Liver / pathology Liver Cirrhosis / blood Liver Cirrhosis / etiology* Liver Cirrhosis / pathology Male Rats Rats, Inbred SHR* / blood Rats, Inbred SHR* / physiology Transaminases / blood Tumor Necrosis Factor-alpha / blood Weight Gain gamma-Glutamyltransferase / blood
IF 2.71
リソース情報
ラット SHRSP5/Dmcr(strainID=737)