Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model.
Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model.
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DOI：
10.1016/j.bbrc.2012.04.087
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发表时间：
2012-05
影响因子：
3.1
通讯作者：
Toshiyuki Oishi;S. Terai;Shinya Kuwashiro;K. Fujisawa;Toshihiko Matsumoto;H. Nishina;I. Sakaida
中科院分区：
文献类型：
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作者：
Toshiyuki Oishi;S. Terai;Shinya Kuwashiro;K. Fujisawa;Toshihiko Matsumoto;H. Nishina;I. Sakaida
我们以前建立了青竹非酒精性脂肪性肝炎(NASH)模型。该模型显示了与人类NASH相似的组织学特征，因此我们使用青冈NASH活性评分(MNAs)来分析药物的影响。本研究分析了小肠胆固醇转运蛋白抑制剂Ezetimibe对NASH的影响。方法：Medaka Nash模型显示脂肪性肝炎伴有D-PAS阳性炎症细胞的浸润。结果与高脂饲料组相比，依折麦布能降低血中总胆固醇和甘油三酯。但在肝脏方面，依折麦布显着降低了肝脏中的脂肪酸含量。给予依折麦布后，肝脏中与脂肪酸代谢相关的基因也减少。肝脏组织学观察显示，肝组织炎性细胞和MNAs数量的增加受到抑制。Ezetimibe通过降低肝脏中的脂肪酸含量，改善青海NASH的疗效。结论Ezetimibe是一种治疗NASH的有效药物。
PURPOSEWe 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.METHODSMedaka 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.RESULTSAs 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.CONCLUSIONEzetimibe was clarified as a useful drug to improve NASH.