PPARα、固醇调节元件结合蛋白和腺苷酸活化蛋白激酶在酒精性脂肪肝发病中作用的研究进展  

Mechanisms of PPARα, sterol regulatory element binding proteins and AMP-activated protein kinase in alcoholic fatty liver diseases:review

作　　者：马萍 彭颖[2] 杨静玉[1] 李晓波[2] MA Ping;PENG Ying;YANG Jing-yu;LI Xiao-bo(School of Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China;School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China)

机构地区：[1]沈阳药科大学中药学院,辽宁沈阳110016 [2]上海交通大学药学院,上海200240

出　　处：《中国药理学与毒理学杂志》2017年第9期900-906,共7页Chinese Journal of Pharmacology and Toxicology

摘　　要：酒精性脂肪肝(AFLD)为酒精性肝损伤的最初症状,对其发生机制的深入研究有助于AFLD的预防和治疗。迄今研究发现,AFLD的发生发展主要与细胞色素P450 2E1、过氧化物酶体增殖物激活受体α(PPARα)、固醇调节元件结合蛋白(SREBP)、腺苷酸活化蛋白激酶(AMPK)、去乙酰化酶1、脂联素和胰岛素等通路相关。研究发现,酒精及代谢产物乙醛直接或间接抑制PPARα和AMPK并激活SREBP蛋白通路,导致肝脂质代谢紊乱、脂肪酸氧化能力降低和脂质堆积,最终形成AFLD。此外,本综述对这3个蛋白作为AFLD治疗靶点的治疗前景予以展望。Alcoholic fatty liver disease（AFLD） is the first step to wards alcoholic liver disease（ALD）. A beffer knowledge of AFLD will contribute to the prevention and therapy of ALD. It has been found that the occurrence and development of AFLD mainly involve the pathways of cytochrome P450（CYP2 E1）, peroxisome proliferator-activated receptor α（PPARα）, sterol regulatory element-binding proteins（SREBPs）, AMP-activated protein kinase（AMPK）, sirtuin 1（SIRT1）, adiponectin and insulin. This review focuses on the importance of PPARα, SREBPs and AMPK pathway in alcoholic steatosis. It′s reported that alcohol and its metabolite acetaldehyde inhibit PPARα and AMPK, and activate SREBP protein directly or indirectly, leading to liver lipid metabolic disorders, reducing the ability of fatty acid oxidation, causing lipid accumulation, and eventually inducing AFLD. Additionally, this review outlines the prospect of a therapeutics of AFLD targetting PPARα, SREBPs and AMPK.

关 键 词：酒精性肝疾病 腺苷酸活化蛋白激酶 PPARΑ 胆固醇调节元件结合蛋白质类 

分 类 号：R575.5[医药卫生—消化系统]