胰升糖素样肽1受体激动剂调节糖尿病合并非酒精性肝病大鼠胰岛素抵抗及肝脏氧化应激损伤的实验研究  

Experimental study on the glucagon-likepeptide 1 receptor agonist modulation of insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease

作　　者：李津[1] 易志刚[1] 郭文安[1] 郭南京[1] 朱雨霏[1] 黄滨 

机构地区：[1]厦门大学附属第一医院保健病房,361003 [2]厦门医学院临床医学系,361003

出　　处：《中华内分泌代谢杂志》2017年第3期228-232,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：福建省卫生厅青年科研课题（2013-2-87）

摘　　要：研究胰升糖素样肽1（GLP-1）受体激动剂利拉鲁肽对糖尿病合并非酒精性脂肪性肝病（NAFLD）大鼠胰岛素抵抗及肝脏氧化应激损伤的影响。选择雄性SD大鼠36只作为实验动物，随机分为对照组、模型组以及GLP-1组，对照组给予常规饲料喂养及生理盐水腹腔注射，模型组给予高脂饲料喂养及生理盐水腹腔注射，GLP-1组给予高脂饲料喂养及利拉鲁肽腹腔注射。治疗后4周时，评估胰岛素抵抗程度、脂质代谢情况、肝损伤程度以及氧化应激反应程度。模型组大鼠血清中空腹血糖、空腹胰岛素、总胆固醇、三酰甘油、谷丙转氨酶（ALT）、谷草转氨酶（AST）含量以及肝脏组织中总胆固醇、三酰甘油含量以及稳态模型评估的胰岛素抵抗指数（HOMA-IR）水平均显著高于对照组，胰岛素混合敏感指数（ISIcomp）水平显著低于对照组；GLP-1组大鼠的血清中空腹血糖、空腹胰岛素、总胆固醇、三酰甘油、ALT、AST含量以及肝脏组织中总胆固醇、三酰甘油含量以及HOMA-IR水平均显著低于模型组，ISIcomp水平显著高于模型组；模型组大鼠肝脏组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、髓过氧化物酶（CAT）的含量显著低于对照组，丙二醛的含量以及SOD、GSH-Px、CAT、NF-E2相关因子2（Nrf-2）、抗氧化反应元件（ARE）、血红素加氧酶l（HO-1）、醌氧化还原酶1（NQO-1）、谷胱甘肽巯基转移酶（GST）的mRNA表达量显著高于对照组；GLP-1组大鼠肝脏组织中SOD、GSH-Px、CAT的含量以及SOD、GSH-Px、CAT、Nrf-2、ARE、HO-1、NQO-1、GST的mRNA表达量显著高于模型组，丙二醛的含量显著低于模型组。GLP-1受体激动剂对糖尿病合并NAFLD大鼠的胰岛素抵抗以及肝脏氧化应激损伤具有改善作用。To study the effect of glucagon-likepeptide 1（GLP-1）receptor agonist on insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease. 36 male SD rats were served as the experimental animal and randomly divided into control group, model group, and GLP-1 group. The rats of control group were given routine diet with intraperitoneal injection of normal saline, those in model group were given high fat diet and intraperitoneal injection of normal saline, while GLP-1 group rats were fed with high fat diet and intraperitoneal injection of liraglutide. After 4 weeks of treatment, insulin resistance, lipid metabolism, liver injury and oxidative stress were all assessed. Serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, alanine transaminase（ALT）, aspartate transaminase（AST）levels and total cholesterol, triglyceride contents in liver tissue, and as well as homeostasis model assessment for insulin resistance（HOMA-IR）levels of model group were significantly higher than those of control group, complex insulin sensitivity index（ISIcomp）level was significantly lower than that of control group; serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, ALT, AST contents and HOMA-IR levels of GLP-1 group were significantly lower than those of model group, ISIcomp level was significantly higher than that of model group; superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px）, catalase（CAT）contents in liver tissue of model group were significantly lower, while malondialdehyde content and SOD, GSH-Px, CAT, NF-E2 related factor-2（Nrf-2）, antioxidant response element（ARE）, heme oxygenase-1（HO-1）, quinone oxidoreductase-1（NQO-1）, glutathione thiol transferase（GST）mRNA expression were significantly higher than control group; SOD, GSH-Px, CAT contents and SOD, GSH-Px, CAT, Nrf-2, ARE, HO-1, NQO-1, GST mRNA expression in the liver tissue of GLP-1 group were significantly high

关 键 词：糖尿病 2型 非酒精性脂肪性肝病 胰升糖素样肽1 胰岛素抵抗 氧化应激 

分 类 号：R575.5[医药卫生—消化系统] R587.1[医药卫生—内科学]