利拉鲁肽对非酒精性脂肪肝大鼠ERp46蛋白和脂联素及氧化应激的影响  

Effects of liraglutide on ERp46 protein,adiponectin and oxidative stress in rats with non-alcoholic fatty liver disease

作　　者：王爱芳 钟兴[1] 潘天荣[1] Wang Aifang;Zhong Xing;Pan Tianrong(Dept of Endoccrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601)

机构地区：[1]安徽医科大学第二附属医院内分泌科,合肥230601

出　　处：《安徽医科大学学报》2020年第2期249-253,共5页Acta Universitatis Medicinalis Anhui

基　　金：2015年公益性技术应用研究联动计划项目(编号:15011d04042)。

摘　　要：目的研究利拉鲁肽对非酒精性脂肪肝大鼠肝组织ERp46蛋白和脂联素及氧化应激的影响,探讨利拉鲁肽改善脂肪肝的可能机制。方法雄性SD大鼠32只,随机分成高脂组20只与正常对照组12只,高脂饮食12周建立非酒精性脂肪肝病模型,再随机分为利拉鲁肽组和安慰剂组,分别予利拉鲁肽[0.6 mg/(kg·d)]和等体积的生理盐水皮下注射;28周末处死大鼠,称得体质量、肝脏质量,检测生化指标及炎症因子水平,肝组织行苏木精-伊红染色;应用实时PCR和Western blot方法检测肝组织ERp46 mRNA和蛋白的表达。结果与安慰剂组比较,利拉鲁肽组大鼠肝组织ERp46和脂联素表达水平升高,体质量、肝指数、谷丙转氨酶、空腹胰岛素、胰岛素抵抗指数、胆固醇、甘油三酯、低密度脂蛋白及肝匀浆甘油三酯、胆固醇、游离脂肪酸、肿瘤坏死因子α、丙二醛下降,肝匀浆超氧化物歧化酶升高,肝脏脂肪变性程度减轻(P<0.05)。结论利拉鲁肽改善非酒精性脂肪肝的机制可能与利拉鲁肽上调肝组织ERp46蛋白表达和脂联素水平,抑制内质网应激和减轻肝组织氧化应激有关。Objective To investigate the effects of liraglutide on ERp46 protein,adiponectin and oxidative stress in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD),and to explore the possible mechanism of liraglutide in improving fatty liver.Methods Thirty two male rats were randomly divided into high-fat diet group(HFD,n=20)and normal diet group(ND,n=12).After NAFLD models were successfully established by high-fat diet for 12 weeks,HFD were randomly divided into liraglutide group and placebo group,and hypodermic injection of liraglutide 0.6 mg/(kg·d)and isopyknic saline respectively.Rats were all killed at the end of 28 weeks.The levels of weight,liver mass,biochemical index and inflammatory factors were measured,and liver tissues were stained with hematoxylin-eosin.Real-time PCR and Western blot were used to detect the expression of ERp46 mRNA and protein in liver tissue.Results Compared with placebo group,the expression levels of ERp46 and adiponectin in liver tissue of liraglutide group were increased,and the body weight,liver index,alanine aminotransferase,fasting insulin,insulin resistance index,cholesterol,triglyceride,low densith lipoprotein,and the liver levels of triglyceride,cholesterol,free fatty acids,tumor necrosis factorαand malonaldehyde decreased,the hepatic homogenate superoxide dismutase(SOD)increased and the degree of hepatic steatosis decreased(P<0.05).Conclusion The mechanism of liraglutide in improving non-alcoholic fatty liver may be related to the up-regulation of ERp46 protein expression and adiponectin level in liver tissue,and inhibition of endoplasmic reticulum stress and alleviation of oxidative stress in liver tissue.

关 键 词：利拉鲁肽 非酒精性脂肪肝病 ERp46 脂联素 超氧化物岐化酶 丙二醛 肿瘤坏死因子-α 

分 类 号：R589.2[医药卫生—内分泌]