利拉鲁肽对非酒精性脂肪性肝病大鼠ERp46表达的干预效应  

The influence of liraglutide on ERp46 in non-alcoholic fatty liver disease rats

作　　者：敖娜[1] 杨晶[1] 郑黎黎[1] 马骥 都健[1] 

机构地区：[1]中国医科大学附属第四医院内分泌科,沈阳110032

出　　处：《中华内分泌代谢杂志》2018年第2期144-148,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：辽宁省科技厅公益项目（2014001016）,辽宁省教育厅项目（L2015567）

摘　　要：目的通过研究利拉鲁肽对非酒精性脂肪性肝病大鼠模型下ERp46表达水平的影响，观察该药物的干预作用。 方法将30只雄性SD大鼠分为正常饲料组（NC，n＝10）和高脂饲料组（n＝20），喂养12周后，再将高脂饲料组大鼠分为高脂组（HF，n＝10）和利拉鲁肽组（100L，n＝10），分别以生理盐水和100 μg/kg利拉鲁肽干预4周，行肝脏苏木素-伊红染色、油红染色、肝脏三酰甘油检测、正常葡萄糖-高胰岛素钳夹试验，TUNEL染色，分别应用实时PCR和Western印迹方法检测ERp46 mRNA和蛋白的表达。 结果HF组大鼠肝脏组织发生脂肪变性、胰岛素抵抗，肝细胞发生凋亡，肝脏组织中ERp46 mRNA和蛋白水平均显著低于对照组（P〈0.05）。利拉鲁肽治疗4周后，同高脂组比较，肝脏脂肪变性、胰岛素抵抗均得到改善，肝细胞凋亡率下降，肝脏组织ERp46 mRNA和蛋白水平升高（P〈0.05）。并且ERp46蛋白表达与肝细胞凋亡率呈负相关（P〈0.05），与葡萄糖输注率呈正相关（P〈0.05）。 结论利拉鲁肽可能通过上调ERp46的表达而起到改善NAFLD大鼠胰岛素抵抗和肝细胞凋亡的作用。Objective Rats were fed with high-fat diet and were successfully induced the models with non- alcoholic fatty liver disease, and to investigate the effects of liraglutide on the expression of ERp46. Methods Thirty male Sprague-Dawley rats were assigned to normal chow group（ NC, n = 10） and high-fat diet group（n=20） , after 12 weeks, the high-fat diet group rats were divided into high-fat diet group（ HF, n = 10） and liraglutide group（ 100L, n= 10 ） and treated with normal saline and liraglutide （ 100 μg/kg） for4 weeks respectively. Liver tissues were measured by hematoxylin-eosin （ HE ）, Oil Red O staining, hepatic triglyceride （ TG）, and hyperinsulinemic-euglycemic clamp test（ HECT）. Hepatocyte apoptosis rate were evaluated by TdT-mediated dUTP nick-end labeling（ TUNEL）, and the expressions of ERp46 mRNA and protein were measured. Results Compared with the NC group, the liver tissues in the HF group have steatosis, insulin resistance, and the percentage of apoptosis was significantly increased. ERp46 mRNA and protein expressions were decreased （ P〈O. 05 ）. Compared with the HF group, liraglutide treatment was sufficient to reduce steatosis, insulin resistance, apoptosis, and increase the ERp46 mRNA and protein （ P〈0.05 ）. Furthermore, the expression of ERp46 protein in the liver was negatively correlated with hepatocyte apoptosis rate, and positive correlated with glucose infusion rate （ GIR, P 〈 0. 05 ）. Conclusion Liraglutide may up-regulate the expression of ERp46 to improve IR and hepatocyte apoptosis in NAFLD rats.

关 键 词：利拉鲁肽 非酒精性脂肪性肝病 胰岛素抵抗 ERp46 细胞凋亡 

分 类 号：R575.5[医药卫生—消化系统]