伽马氨基丁酸抑制高脂诱导肥胖小鼠肝脏氧化应激及肝脂肪变性  

GABA Inhibits the Liver Oxidative Stress and Hepatic Steatosis in High-Fat Diet-Fed Obese Mice

作　　者：谢振兴[1,2] 李秀[3] 耿旭[2] 夏淑芳[3] 乐国伟[1,3] 施用晖[1,3] 

机构地区：[1]食品科学与技术国家重点实验室江南大学,江苏无锡214122 [2]河南大学医学院,河南开封475001 [3]江南大学食品学院,江苏无锡214122

出　　处：《食品与生物技术学报》2015年第6期613-620,共8页Journal of Food Science and Biotechnology

基　　金：国家"十二五"科技支撑计划项目(2012BAK17B09 2013BAD19B09)

摘　　要：研究伽马氨基丁酸(GABA)对高脂日粮小鼠肝脏氧化应激、脂肪变性及脂代谢相关基因表达的影响。采用50只C57BL/6雄性小鼠,随机分为5组:正常组(正常日粮),高脂组(高脂日粮),3个GABA处理组(饮水中分别添加质量分数0.2%、0.12%和0.06%GABA)。实验18周后,测定小鼠肝脏组织自由基水平、抗氧化酶活性、脂肪和糖原含量以及血浆谷丙转氨酶、谷草转氨酶活性,同时对肝组织形态进行观察,并用RT-PCR检测肝脏SREBP-1c、FAS、ACC1、PPARα、Cpt1a和PGC-1α的表达。结果显示,高脂日粮显著升高小鼠肝脏质量、肝指数、肝脏甘油三酯和胆固醇含量,降低肝脏功能(P<0.05);添加质量分数0.2%、0.12%和0.06%GABA可显著降低肝脏质量和肝指数,质量分数0.2%、0.12%GABA显著抑制肝脏脂肪变性和改善肝功能(P<0.05)。相比正常组,高脂组动物肝组织中抗氧化酶活性显著降低,自由基和丙二醛含量显著升高(P<0.05);质量分数0.2%、0.12%GABA可显著缓解氧化应激。高脂日粮小鼠肝脏PPARα、Cpt1a和PGC-1α表达显著下调,SREBP-1c、FAS和ACC1表达显著上调(P<0.05),而添加质量分数0.2%、0.12%GABA可显著缓解高脂造成的上述基因表达的变化。因此,高脂日粮导致小鼠肝脏氧化应激、脂肪变性及肝功能损伤,一定剂量GABA可改善肝脏氧化还原状态和脂肪变性,从而预防脂肪肝发生。The effects of gamma-aminobutyric acid （γ-aminobutyric acid, GABA） on oxidative stress,liver function, hepatic steatosis and lipid metabolism-related gene expression were studied in the liver of high-fat diet fed mice. 50 C57BL/ 6 male mice were randomly divided into five groups： normal group （normal diet）, high fat diet group （high fat diet）, and three GABA groups （0.2%, 0.12% and 0.06%GABA in drinking water, respectively）. After 18 weeks, reactive oxygen species （ROS） levels, antioxidant enzyme activities, contents of lipid and glycogen in liver and plasma activities of alanine aminotransferase and aspartate aminotransferase were measured. In addition, the morphological features of liver tissue were observed and the expressions of SREBP-1c, FAS, ACC1, PPARα, Cpt1a and the PGC-1αin liver were measured by using of RT-PCR. The results showed that in high-fat diet fed mice, liver weight, liver index, triglyceride and cholesterol contents in liver increased significantly with damaged liver function;0.2%, 0.12%and 0.06%GABA treatments can significantly reduce liver weight and liver index; 0.2%, 0.12% GABA treatments significantly inhibited hepatic steatosis and improved liver function. Compared with that of in normal group, high fat diet treatment significantly reduced antioxidant enzyme activities and increased ROS and malondialdehyde （MDA） contents;0.2%and 0.12%GABA treatments significantly alleviated oxidative stress. In liver of high-fat diet fed mice, expressions of PPARα, Cpt1a PGC- 1α were significantly reduced, while, expressions of SREBP-1c, FAS and ACC1 were remarkably increased, but both 0.2% and 0.12%GABA supplements can significantly alleviate the gene expression changes that high fat caused. Thus, high-fat diet treatment led to oxidative stress in liver, steatosis and damaged liver function. Meanwhile, a certain dose of GABA can improve redox status and fat metabolisms, thereby preventing the occurrence of fatty liver.

关 键 词：高脂 氧化应激 脂肪肝 肝脂肪变性 伽马氨基丁酸 

分 类 号：R589.2[医药卫生—内分泌]