利拉鲁肽调节2型糖尿病大鼠肝脏脂质沉积的机制探讨  

Mechanism of Liraglutide regulating hepatic steatosis in rats with type 2 diabetes mellitus

作　　者：郭皓宇[1] 曾亚[1] 申月明[1] 王俊[1] 侯周华[2] Hao-yu Guo;Ya Zeng;Yue-ming Shen;Jun Wang;Zhou-hua Hou(Department of Gastroenterology,Changsha Central Hospital,Changsha,Hunan 410004,China;Department of Infectious Diseases,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China)

机构地区：[1]湖南省长沙市中心医院消化科,湖南长沙410004 [2]中南大学湘雅医院感染病科,湖南长沙410008

出　　处：《中国现代医学杂志》2018年第32期1-5,共5页China Journal of Modern Medicine

基　　金：湖南省科技厅科技计划项目(No:2013SK3025)

摘　　要：目的探讨利拉鲁肽调节2型糖尿病(T2DM)大鼠肝脏脂质沉积的机制。方法采用高脂饮食联合链脲佐菌素诱导复制T2DM大鼠模型,随机分组为糖尿病组、利拉鲁肽组、对照组,每组10只。通过肝脏形态学检测观察大鼠肝细胞脂质沉积改善情况;血液学检测观察血清脂联素水平的变化;Western blot检测肝脏AMPK、Thr172p-AMPK、SREBP1蛋白表达水平的变化。结果糖尿病组大鼠较对照组大鼠肝细胞脂质沉积增多(P <0.05),经利拉鲁肽治疗后肝细胞脂质沉积减小(P <0.05);与对照组比较,糖尿病组血清脂联素水平升高(P<0.05)。与对照组比较,糖尿病组大鼠肝脏Thr172p-AMPK/AMPK降低(P<0.05),SREBP-1c表达水平升高(P <0.05)。利拉鲁肽治疗后,Thr172p-AMPK/AMPK升高(P <0.05),SREBP-1c表达水平降低(P <0.05)。结论利拉鲁肽可通过抑制脂质合成,进而改善T2DM大鼠的肝脏脂质沉积。Objective To investigate the mechanism of Liraglutide regulating hepatic steatosis in rats with type 2 diabetes mellitus(DM).Methods A high-fat diet plus a low-dose streptozotocin was implemented to create a type 2 diabetic rat model.The rats were randomly divided into a DM group and a Liraglutide group,and healthy rats were as normal control group(NC group),each group had 10 rats.Liver fatty changes were evaluated with oil red O staining.Fasting plasma adiponectin concentration was measured by ELISA.Protein expression levels of AMPactivated protein kinase(AMPK),phosphorylated AMPK on threonine 172(Thr172p-AMPK),and sterol regulatory element-binding protein 1c(SREBP-1c)in 1iver homogenate were detected by Western blot.ANOVA or LSD test was used for data analysis.Results Compared with the NC group,the presence of cytoplasmic lipid deposits in the DM group was confirmed by oil red O staining(P<0.05).Lipids deposition in hepatocytes was significanly alleviated in the Liraglutide group as compared to the DM group(P<0.05).Compared to the NC group,plasma adiponectin level was significantly increased(P<0.05),Thr172p-AMPK/AMPK in the rat liver was significantly reduced(P<0.05),and SREBP-1c expression was increased in the DM group(P<0.05).After Liraglutide therapy Thr172p-AMPK/AMPK was significantly increased,SREBP-1c expression was significantly declined(P<0.05).Conclusions Liraglutide ameliorates hepatic steatosis probably by inhibiting lipogenesis in rats.

关 键 词：脂质沉积 2型糖尿病 利拉鲁肽 

分 类 号：R587.1[医药卫生—内分泌]