槲皮素对慢性酒精暴露小鼠肝脏自噬的调控  

Quercetin alleviates chronic alcohol exposure induced liver autophagy dysfunction

作　　者：李艳艳 于微[1] 冯里茹[1] 郭小萍 姚平[2] 王俊[1] 

机构地区：[1]深圳市慢性病防治中心理化检验科,广东深圳518020 [2]华中科技大学同济医学院公共卫生学院营养与食品卫生学系,湖北武汉430030

出　　处：《中国药理学通报》2018年第1期82-86,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81402673);广东省医学基金资助项目(No A2016130;A2017206);深圳市科技计划项目(No JCYJ20160428145633098);深圳市卫生计生系统科研项目(No 201605016)

摘　　要：目的探讨慢性酒精暴露对肝脏溶酶体自噬的影响及槲皮素的拮抗效应。方法成年♂C57BL/6J小鼠按体质量随机分为4组,即正常对照组(Con)、酒精组(Eth)、酒精+槲皮素组(Eth+Qu)、槲皮素对照组(Qu)。各组小鼠等能量配对喂养15周,检测肝脏损伤相关指标、溶酶体损伤及自噬标志蛋白的表达。结果与正常对照组相比,长期酒精摄入引起肝脏严重的脂质沉积、氧化损伤(MDA水平明显升高,而GSH水平明显降低)、血清ALT、AST水平明显增加;肝细胞中自噬体标志蛋白LC3-II及自噬底物蛋白p62异常升高;Lyso-Tracker Red染色后,酒精组肝脏荧光强度明显减弱,胞质中cathepsin B活性明显升高;此外,自噬体与溶酶体融合关键蛋白溶酶体相关膜蛋白2A(LAMP2A)的表达也明显下降;槲皮素干预减轻了溶酶体损伤、改善了自噬体的积累,降低了LC3-II与p62的蓄积,促进了自噬体与溶酶体的融合,同时上调LAMP2A的表达,肝脏损伤明显缓解。结论槲皮素可能通过减轻溶酶体损伤、上调自噬体与溶酶体融合关键蛋白LAMP2A水平,缓解慢性酒精暴露所致肝脏自噬抑制,从而减轻酒精性肝损伤。Aim To investigate the potential protective effect of quercetin on chronic ethanol exposure induced autophagy dysfunction. Methods The male C57 BL/6 J mice were divided randomly into four groups: Normal control group( Con); Ethanol group( Eth); Ethanol plus Quercetin group( Eth + Qu); Quercetin control group( Qu). The mice were pair-fed with either regular or ethanol-containing Lieber De Carli liquids diets for 15 weeks and the related parameters were assayed. Result Compared to Con group,chronic ethanol feeding led to serious aminotransferases leakage,hepatic lipid accumulation,and liver oxidative damage. Additionally,long-term ethanol exposure caused lysosome damage,cathepsin B leakage to cytoplasm and decreased the expression of LAMP2 A which was the key protein for the autophagosome-lysosome fusion.As expect,quercetin supplementation evidently alleviated lysosome damage and decreased the abnormal LC3-II and p62 accumulation,accelerated the autophagosome-lysosome fusion and increased the expression of LAMP2 A. Conclusion Quercetin may alleviate the liver injury induced by chronic alcohol exposure by ameliorating the lysosomal damage and up-regulating LAMP2 A expression.

关 键 词：酒精性肝病 肝损伤 槲皮素 溶酶体 自噬作用 LAMP2A 

分 类 号：R-332[医药卫生] R284.1