南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (11): 1661-.

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GLP-1对非酒精性脂肪肝大鼠肝氧化应激及TNF-α、TGF-β1的影响

高慧亭,徐丽姝,李东风,关丽嫦,邓卫平   

  • 出版日期:2013-11-20 发布日期:2013-11-20

Effects of glucagon-like peptide-1 on liver oxidative stress, TNF-α and TGF-β1 in rats with non-alcoholic fatty liver disease

  • Online:2013-11-20 Published:2013-11-20

摘要: 目的观察胰高血糖素样肽-1(GLP-1)对非酒精性脂肪肝大鼠肝氧化应激及肿瘤坏死因子α(TNF-α)、转换生长因子β1
(TGF-β1)的影响。方法雄性SD大鼠30只,随机分为3组,分别予普通饮食10只(ND组)、高脂饮食10只(HFD组)、高脂饮食
加利拉鲁肽腹腔注射10只(GLP-1组)。高脂饮食12周建立大鼠NAFLD模型,建模成功后GLP-1组予利拉鲁肽腹腔注射治疗4
周。16周末处死各组大鼠,生物化学法检测血清ALT、血清和肝组织甘油三酯(TG)、总胆固醇(TC),分光光度计测定肝匀浆超
氧化物歧化酶(SOD)、丙二醛(MAD)及FFAs,酶联免疫吸附法测定血清TGF-β1、肝匀浆TNF-α。结果与ND组比较,HFD组
大鼠体质量、肝指数、血清ALT、TG、TC、TGF-β1及肝匀浆TG、TC、MAD、FFAs 、TNF-α均明显升高(P>0.05),肝匀浆SOD活力
明显降低(P<0.05),肝脏脂肪变性程度和炎症活动度显著增高(P<0.05);而与HFD组比较,GLP-1组可促进上述指标恢复(P<
0.05)。结论利拉鲁肽可以减轻高脂饮食诱导肝脂肪变,改善氧应激及脂质过氧化,降低TNF-α及TGF-β1的含量,有可能作为
治疗非酒精性脂肪肝病的有效药物。

Abstract: Objective To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-β1
in rats with diet-induced non-alcoholic fatty liver disease (NAFLD). Methods Thirty male rats were randomly divided into 3
equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of
liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues
for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic
biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α
in the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA. Results Compared with ND group, HFD
group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD,
FFAs, and TNF-a in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation
activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05). Conclusion
Liraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease
TGF-β1 and TNF-a levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.