艾塞那肽对非酒精性脂肪肝大鼠肝脏NF-κB、TNF-α、TGF-β_1表达的影响

Effect of exenatide on the expressions of liver NF-κB,TNF-α and TGF-β_1 in rats with non-alcoholic fatty liver disease

目的观察艾塞那肽(Exenatide)对高脂诱导大鼠非酒精性脂肪性肝病(NAFLD)的作用。方法建立SD大鼠NAFLD模型(HF组),高脂喂养SD大鼠8周后予艾塞那肽(10μg/kg)干预8周(HF+Exe组),观察肝脏病理变化及相关检测。结果 HF+Exe组大鼠体重、肝指数(肝湿重/大鼠体重)、肝脏TG、FFA、OGTT、2hPG、FIns、胰岛素抵抗指数(HOMA-IR)、TG、LDL-C、丙氨酸转氨酶(ALT)较HF组明显下降(P<0.01或P<0.05);HF组大鼠存在明显肝脏脂肪沉积,HF+Exe组大鼠肝脏脂肪沉积明显减少(P<0.01);HF+Exe组肝脏核转录因子(NF-κB)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)mR-NA表达较HF组明显下降(P<0.05)。结论艾塞那肽改善高脂诱导大鼠糖脂代谢、肝功能、减少肝脏NF-κB、TNF-α、TGF-β1表达,对NAFLD有一定防治作用。

Objective To investigate the effect of exenatide on expresions of 1iver NF-κB,TNF-α and TGF-β1 in rats with non-alcoholic fatty liver disease（NAFLD）.Methods The high fat diet-induced NAFLD rat models were established（group HF）.After the high fat diet for 8 weeks,the rats were given exenatide（10 μg/kg） intervention for 8 weeks（group HF＋Exe）.Observations on the hepatic pathological changes and other related inspections were performed for studying the effect of treatment.Results The body weight,liver index（liver weight / rat weight）,liver triglyceride（TG）,serum free fatty acid（FFA）,2 hours serum glucose after oral glucose tolerance test（OGTT）,serum fasting insulin（FIns）,insulin resistance index（HOMA-IR）,serum TG,low density lipoprotein cholesterol（LDL-C）,and serum alanineaminotransferase（ALT） were all significantly lowered in the group HF＋Exe than in the group HF（P〈0.01,P〈0.05）.In the group HF,there appeared a significant steatosis,whilst the steatosis was significantly improved in group HF＋Exe（P〈0.01）.mRNA expression levels of nuclear factor-κB（NF-κB）,tumor necrosis factor-α（TNF-α）,and transforming growth factor-β1（TGF-β1） in liver were significantly decreased in the group HF＋Exe than in the group HF（P〈0.01）.Conclusion Exenatide improves the glucose and lipid metabolisms,restores the liver function,and decreases expressions in the liver NF-κB,TNF-α,and TGF-β1 in high fat diet rats,thus preventing the occurrence and progression of NAFLD in rats.