High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats
High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats
复制标题
DOI：
10.1111/hepr.12358
复制
发表时间：
2015-04-01
影响因子：
4.2
通讯作者：
Omagari, Katsuhisa
中科院分区：
文献类型：
--
作者：
Ichimura, Mayuko;Kawase, Miku;Omagari, Katsuhisa
目的纤维化的发展被认为是非酒精性脂肪性肝炎（NASH）发展到肝病终末期（包括肝硬化）的一个重要阶段。然而，很少有小动物模型显示nash相关纤维化。我们的目标是用基因正常的大鼠建立一个快速进展为纤维化的NASH饮食模型。方法9周龄雄性Sprague-Dawley大鼠分别饲喂正常、高脂（HF）或两种高脂高胆固醇（HFC）饲料9周（各n=5）。所有含氢氟烃的饮食都含有1.25%或2.5%的胆固醇。结果HF组大鼠在18周龄时出现轻度脂肪变性和炎症，但无纤维化，而HFC组大鼠均出现明显脂肪变性和炎症，肝细胞肿胀和纤维化。给予含2.5%胆固醇的HFC饮食的5只大鼠中有2只（40%）进展为肝硬化。给予HFC的大鼠肝脏总胆固醇水平明显高于正常或HF饮食。HFC饮食显著且剂量依赖性地降低微粒体甘油三酯转移蛋白的表达。胆固醇倾向于抑制肉碱棕榈酰基转移酶活性和三磷酸腺苷结合盒转运体G5的表达。在HF日粮中添加胆固醇在分子水平上改变了肝脏脂质代谢。结论HFC饮食可诱导sd - dawley大鼠在9周内出现NASH的肝脏特征并最终进展为肝硬化。
AimThe development of fibrosis is considered an important phase in the progress of non-alcoholic steatohepatitis (NASH) towards the end stage of liver disease, including cirrhosis. However, few small animal models can display NASH-associated fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis using genetically normal rats.MethodsNine-week-old male Sprague-Dawley rats were fed with normal, high-fat (HF), or two types of high-fat and high-cholesterol (HFC) diets for 9 weeks (n=5 each). All HFC diets contained 1.25% or 2.5% cholesterol.ResultsThe rats fed with the HF diet developed mild steatosis and inflammation without fibrosis at 18 weeks of age, whereas all rats given the HFC diet developed obvious steatosis and inflammation with hepatocyte ballooning and fibrosis. Two of five (40%) rats given the HFC diet containing 2.5% cholesterol progressed to liver cirrhosis. Hepatic total cholesterol levels were significantly higher in rats given the HFC, than the normal or HF diets. The HFC diet significantly and dose-dependently decreased microsomal triglyceride transfer protein expression. Cholesterol tended to suppress carnitine palmitoyltransferase activity and adenosine triphosphate-binding cassette transporter G5 expression. Adding cholesterol to the HF diet modified hepatic lipid metabolism at the molecular level.ConclusionThe HFC diet induced hepatic features of NASH and eventually progressed cirrhosis in Sprague-Dawley rats within 9 weeks.