Department of Gastroenterology & Hepatology, Yamaguchi University, Graduated School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
Biochem Biophys Res Commun. 2012 May 25;422(1):22-7. doi: 10.1016/j.bbrc.2012.04.087. Epub 2012 Apr 25.
We previously developed medaka non-alcoholic steatohepatitis (NASH) model. The model showed similar histology with human NASH so we analyzed the effect of drug using medaka NASH activity score (MNAS). In this study we analyzed the effect of ezetimibe, a small intestine cholesterol transporter inhibitor, on NASH.
Medaka NASH model showed steatohepatits with infiltration of D-PAS positive inflammatory cell. In this study we induced medaka NASH and compared the effect of ezetimibe on medaka NASH by HFD.
As compared with the HFD group, ezetimibe reduced total cholesterol and triacyglycerol in the blood. But concerning with liver quantity of fatty acids in the liver were significantly decreased by ezetimibe. Genes related with fatty acid metabolism in liver was also decreased by ezetimibe administration. On histological observations of the liver, increases in the number of inflammatory cells and MNAS were inhibited. With this decrease of fatty acid in liver, medaka NASH was improved by ezetimibe.
Ezetimibe was clarified as a useful drug to improve NASH.
我们之前开发了一种非酒精性脂肪性肝炎(NASH)的斑马鱼模型。该模型的组织学表现与人 NASH 相似,因此我们使用斑马鱼 NASH 活性评分(MNAS)分析了药物的作用。在这项研究中,我们分析了抑制小肠胆固醇转运蛋白的依折麦布对 NASH 的作用。
斑马鱼 NASH 模型显示出伴有 D-PAS 阳性炎症细胞浸润的肝脂肪变性。在本研究中,我们通过高脂肪饮食(HFD)诱导了斑马鱼 NASH,并比较了依折麦布对斑马鱼 NASH 的作用。
与 HFD 组相比,依折麦布降低了血液中的总胆固醇和三酰甘油。但依折麦布显著降低了肝脏中的脂肪酸含量。肝脏中与脂肪酸代谢相关的基因也因依折麦布的给药而减少。在肝脏的组织学观察中,炎症细胞数量和 MNAS 的增加受到抑制。随着肝脏中脂肪酸的减少,依折麦布改善了斑马鱼 NASH。
依折麦布被证实是一种改善 NASH 的有效药物。