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GO-CoA-Tat改善脂肪肝小鼠脂质代谢和氧化应激

GO-CoA-Tat improves lipid metabolism and oxidative stress in mice with fatty liver disease

    摘要
  • 摘要:
    目的  探讨饥饿素O-酰基转移酶（ghrelin O-acyltransferase，GOAT）抑制剂GO-CoA-Tat对高脂饮食（high-fat diet，HFD）诱导的非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）小鼠脂质代谢和氧化应激的影响。
    方法  选择C57BL/6雄性小鼠24只，分为对照组、HFD组和GO-CoA-Tat组，每组8只。对照组给予标准饮食，HFD组和GO-CoA-Tat组均给予HFD，GO-CoA-Tat组喂养第3周起每天腹腔注射GO-CoA-Tat。每周测量小鼠食物摄入量和小鼠体质量。喂养8周后采集血清及肝脏样本，测量肝脏质量，并采用油红O染色检测肝脏脂滴形成情况；检测并比较3组小鼠血清三酰甘油（triglyceride，TG）、总胆固醇（total cholesterol，TC）、丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）和肝脏谷胱甘肽（glutathione，GSH）、超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA）。
    结果  HFD组小鼠喂养8周后出现明显的肝脏脂肪变性；与HFD组相比，GO-CoA-Tat组脂肪变性明显缓解。与HFD组相比，GO-CoA-Tat组小鼠食物摄入量减少、体质量减小、肝脏质量减小（P < 0.05）。与HFD组相比，GO-CoA-Tat组小鼠肝脏TG含量降低，血清TG和TC降低（P < 0.05）；肝脏GSH、SOD浓度升高（P < 0.01），MDA浓度下降（P=0.005）；血清ALT和AST降低（P < 0.05）。
    结论  GO-CoA-Tat可改善NAFLD小鼠肝脏的脂质代谢和氧化应激，从而发挥肝脏保护作用。

     

    Abstract:
    Objective  To investigate the effects of GO-CoA-Tat, an inhibitor of ghrelin O-acyltransferase (GOAT), on lipid metabolism and oxidative stress in mice with non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD).
    Methods  Twenty-four C57BL/6 male mice were selected and divided into control group, HFD group and GO-CoA-Tat group, with 8 mice in each group. The mice in control group was given standard diet, the mice in HFD group and GO-CoA-Tat group were given HFD, and the mice in GO-CoA-Tat group was given daily intraperitoneal injection of GO-CoA-Tat from 3rd week of feeding. Food intake and body mass of mice were measured weekly. After 8 weeks, serum and liver samples were collected, liver weight was measured, and fat droplets were detected by hepatocyte oil red O staining; biochemical indexes such as serum triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress indexes of liver such as glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured.
    Results  Hepatic steatosis was observed after feeding with HFD for 8 weeks, which was significantly relieved in GO-CoA-Tat group compared with HFD group. Compared with HFD group, the food intake, body weight and liver weight of mice in GO-CoA-Tat group decreased (P < 0.05). Compared with HFD group, the content of TG in liver of mice in GO-CoA-Tat group decreased, the concentrations of serum TG and TC decreased (P < 0.05), and the concentrations of liver GSH and SOD increased (P < 0.01), liver MDA decreased (P=0.005), and the serum ALT and AST decreased (P < 0.05).
    Conclusion  GO-CoA-Tat can improve lipid metabolism and oxidative stress in the liver of NAFLD mice, thus play a protective role in the liver.

     

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