摘要
目的探讨γ-氨基丁酸(GABA)通过改善代谢相关脂肪性肝病(MAFLD)减轻饮食诱导的糖脂代谢紊乱的作用机制。方法将24只6周龄的SPF级雄性C57BL/6J小鼠根据随机数字表法将其分为对照组、MAFLD组、干预组-1,干预组-2,每组6只。除对照组外,其余各组以高脂饲料饲喂,对照组饲喂正常小鼠维持饲料,持续12周构建MAFLD小鼠模型。造模成功后,干预组-1、干预组-2小鼠分别给予1、2 g/kg GABA溶入水中灌胃干预,对照组和MAFLD组给予等量生理盐水,灌胃给药4周。每周定点测量各组体重和空腹血糖。GABA干预4周后禁食12 h,麻醉小鼠,取血和肝脏组织。检测肝细胞脂质沉积、糖脂代谢及炎症相关基因和蛋白表达、肝细胞氧化应激水平。结果与对照组比较,MAFLD组小鼠体重、肝重和血糖升高,肝脏脂肪变性,糖异生、脂肪酸合成及炎症相关基因表达上调,AMPKαmRNA表达下调,肝细胞氧化应激水平增加(P<0.05);与MAFLD组比较,干预组-1和干预组-2小鼠体重、肝重和血糖降低,肝脏脂肪变性改善,糖异生、脂肪酸合成及炎症相关基因表达下调,AMPKαmRNA表达上调,肝细胞氧化应激减少(P<0.05);与干预组-1比较,干预组-2小鼠体重、肝重和血糖降低,肝脏脂肪变性,糖异生、脂肪酸合成及炎症相关基因表达下调,AMPKαmRNA表达上调,肝细胞氧化应激减少(P<0.05)。结论GABA可通过抑制肝脏脂肪生成、糖异生、炎症反应和氧化应激,改善机体糖脂代谢紊乱。
Objective To investigate the mechanism by gamma-aminobutyric acid(GABA)alleviates diet-induced glycolipid metabolism disorders by improving metabolic associated fatty liver disease(MAFLD).Methods A total of 24 SPF grade C57BL/6J male mice aged six weeks were divided into control group,MAFLD group,intervention group-1,and intervention group-2 according to the random number table method,with six mice in each group.Except for the control group,the other groups were fed with high-fat diet and the control group was fed with normal mouse maintenance diet for 12 weeks to construct the MAFLD mouse model.After the model was successfully established,the mice in intervention group-1 and intervention group-2 were given 1,2 g/kg GABA dissolved in water for intragastric intervention respectively,and the control group and MAFLD group were given the same amount of normal saline for intragastric administration for four weeks.The weight and fasting blood glucose of each group were measured at a fixed point every week.After GABA intervention for four weeks,the mice were fasted for 12 h,anesthetized,and blood and liver tissues were collected.The expression of genes and proteins related to lipid deposition,glucose and lipid metabolism and inflammation,and hepatic oxidative stress levels were detected.Results Compared with the control group,the body weight,liver weight,and blood glucose of mice in the MAFLD group were increased,liver steatosis,gluconeogenesis,fatty acid synthesis,and inflammation-related gene expression were up-regulated,AMPKαmRNA expression was down-regulated,and the level of oxidative stress in hepatocytes was increased(P<0.05).Compared with MAFLD group,the body weight,liver weight,and blood glucose of mice in intervention group-1 and intervention group-2 were decreased,the hepatic steatosis was improved,the expression of gluconeogenesis,fatty acid synthesis,and inflammation-related genes was down-regulated,the expression of AMPKαmRNA was up-regulated,and the oxidative stress of hepatocytes was decreased(P<0.05).Compared with the intervention group-1,the body weight,liver weight and blood glucose of the intervention group-2 mice were decreased,liver steatosis,gluconeogenesis,fatty acid synthesis,and inflammation-related gene expression were down-regulated,AMPKαmRNA expression was up-regulated,and hepatocyte oxidative stress was reduced(P<0.05).Conclusion GABA can ameliorate the disorder of glycolipid metabolism by inhibiting liver lipogenesis,gluconeogenesis,inflammation,and oxidative stress.
作者
王庆胜
曹杰
袁莉
WANG Qingsheng;CAO Jie;YUAN Li(Department of Radiology,the Third Hospital of Wuhan,Hubei Province,Wuhan430060,China;Department of Endocrinology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei Province,Wuhan430022,China)
出处
《中国医药导报》
2025年第6期25-31,共7页
China Medical Herald
关键词
Γ-氨基丁酸
代谢相关脂肪性肝病
胰岛素抵抗
炎症反应
氧化应激
Gamma-aminobutyric acid
Metabolic associated fatty liver disease
Insulin resistance
Inflammatory res-ponse
