Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease
Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease
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DOI：
10.1016/j.jhep.2009.05.017
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发表时间：
2009-09-01
影响因子：
25.7
通讯作者：
Nakajima, Atsushi
中科院分区：
文献类型：
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作者：
Nozaki, Yuichi;Fujita, Koji;Nakajima, Atsushi
背景/目的：非酒精性脂肪性肝病(NAFLD)是代谢综合征的一种肝脏表现，与肥胖、高脂血症、2型糖尿病和高血压等多种因素密切相关，目前任何单一疗法都难以有效治疗NAFLD。方法：C57BL/6J小鼠分为基础饲料(1113)、高脂饲料(HFD)、高脂饲料加高脂饲料(5 mg/kg/d)、高脂饲料加AC(100 mg/kg/d)、高脂饲料加高脂饲料(EZ+AC)5 mg/kg/d、高脂饲料+阿卡波糖(AC+EZ/AC)治疗24周。结果：EZ与AC长期联合治疗可明显减轻肝脏脂肪变性、炎症和肝纤维化。在HFD诱导的NAFLD小鼠模型中；与单独用药相比，联合用药组小鼠肝脏微粒体甘油三酯转移蛋白(MTP)和过氧化物酶体增殖物激活受体-α1(PPAR-α1)的表达也显著增加，这可能是改善脂代谢紊乱的原因之一。结论：EZ和AC联合治疗24周可改善NAFLD小鼠模型的组织病理学改变。(C)2009年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor.Methods: C57BL/6J mice were divided into five treatment groups as follows: basal diet (1113), high-fat diet (HFD) only, HFD with EZ (5 mg/kg/day), HFD with AC (100 mg/kg/day), and HFD with both EZ and AC for 24 weeks.Results: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha 1 (PPAR-alpha 1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model.Conclusions: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.