Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
Environ Health Prev Med. 2012 May;17(3):173-82. doi: 10.1007/s12199-011-0235-9. Epub 2011 Aug 19.
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.
非酒精性脂肪性肝病在全球范围内不断增加，因此预防措施是当务之急和首要关注点。
本研究旨在开发和阐明自发性高血压大鼠衍生的 SHRSP5/Dmcr 大鼠（一种易发生中风的自发性高血压大鼠）作为一种新的动物模型，用于分析非酒精性脂肪性肝炎和疾病中常观察到的严重纤维化进展的时间进程。
将 10 周龄雄性 SHRSP5/Dmcr 大鼠分为六组：一半喂食高脂肪和高胆固醇饮食（HFC 饮食），另一半喂食易发生中风的饮食（SP 饮食）2、8 和 14 周。
HFC 饮食显著增加了血清转氨酶和γ-谷氨酰转肽酶活性、肿瘤坏死因子-α 水平以及血清和肝脏总胆固醇水平随时间的变化。相反，该饮食降低了血清白蛋白、葡萄糖和脂联素水平，贯穿或在喂养后期，但不影响血清胰岛素水平。组织病理学上，HFC 饮食增加了微泡性脂肪变性，在 2 周时观察到肝脏的局灶或点状坏死伴淋巴细胞浸润，在 8 周时观察到大泡性脂肪变性、气球样肝细胞伴 Mallory-Denk 体形成，在 14 周时观察到多小叶坏死和纤维化。有趣的是，这种纤维化在 14 周时形成了蜂窝状网络。这些变化与非酒精性脂肪性肝炎患者的变化非常相似。
SHRSP5/Dmcr 大鼠似乎是分析 HFC 饮食诱导的脂肪性肝炎和纤维化进展时间依赖性变化的有用模型。
