利拉鲁肽联合维生素D对高脂诱导非酒精性脂肪肝小鼠的影响及机制  

Effects of liraglutide combined with vitamin D on non-alcoholic fatty liver induced by high fat in mice and its mechanism

作　　者：王锋[1] 张海峰[1] WANG Feng;ZHANG Hai-feng(Department of Physiology,Inner Mongolia Medical University,Hohhot 010110,China)

机构地区：[1]内蒙古医科大学生理学教研室,呼和浩特010110

出　　处：《中国应用生理学杂志》2020年第3期261-265,共5页Chinese Journal of Applied Physiology

基　　金：内蒙古医科大学科技百万项目(YKD2016 KJBW018);内蒙古自治区卫生和计划生育委员会科研计划项目(201701046)。

摘　　要：目的:探讨利拉鲁肽联合维生素D对高脂诱导非酒精性脂肪肝(NAFLD)小鼠的影响及其潜在机制。方法:C57BL/6小鼠随机平均分为对照组、NAFLD模型组、利拉鲁肽组、维生素D组和利拉鲁肽联合维生素D组,每组10只。对照组普通饲料连续喂养12周;模型组高脂饲料连续喂养12周;利拉鲁肽组、维生素D组和联合组均高脂饲料连续喂养12周,从第9周起上述3组小鼠分别腹腔注射0.6 mg/(kg·d)利拉鲁肽、灌胃250 mg/(kg·d)维生素D和腹腔注射0.6 mg/(kg·d)利拉鲁肽及灌胃250 mg/(kg·d)维生素D。喂养至12周后,收集各组小鼠血液和肝组织进行生化及病理检测;并采用免疫印迹方法检测各组小鼠肝组织AMP活化蛋白激酶(AMPK)磷酸化水平。结果:与模型组相比,利拉鲁肽或维生素D单独或联合治疗均可改善NAFLD小鼠肝脏脂质积累(甘油三酯:6.0±0.7 vs 3.8±0.3,3.9±0.3和2.1±0.2,P均<0.05;胆固醇:1.4±0.5 vs 0.9±0.2,0.8±0.2和0.5±0.1,P均<0.05)和脂肪变性(NAFLD活动评分:2.4±0.3 vs 1.0±0.2,0.9±0.1和0.6±0.1,P均<0.05);此外与利拉鲁肽或维生素D组相比,利拉鲁肽联合维生素D治疗效果更明显,而且可能与调节胰岛素抵抗和AMPK磷酸化相关。结论:结果表明,维生素D可增强利拉鲁肽对高脂诱导NAFLD的治疗效果,其机制可能与调节胰岛素抵抗和AMPK磷酸化有关。Objective:To investigate the effects of liraglutide combined with vitamin D on high-fat-induced non-alcoholic fatty liver disease(NAFLD)mice and its potential mechanism.Methods:C57BL/6 mice were divided into control group,NAFLD model group,liraglutide group,vitamin D group and liraglutide combined with vitamin D group.Each group consisted of 10 mice.The control group was fed with normal diet for 12 weeks;the model group was fed with high-fat diet for 12 weeks;the liraglutide group,vitamin D group and combined group were fed with high-fat diet for 12 weeks,From the 9th week,the three groups of mice were intraperitoneally injected with liraglutide(0.6 mg/kg),vitamin D(250 mg/(kg·d))by gavage,and combination.After 12 weeks of feeding,the blood and liver tissues of mice in each group were collected for biochemical and pathological examination,and the phosphorylation level of AMP-activated protein kinase(AMPK)in liver tissues of mice in each group was detected by immunoblotting.Results:Liraglutide or vitamin D alone or in combination could improve liver lipid accumulation(triglycerides:6.0±0.7 vs 3.8±0.3,3.9±0.3 and 2.1±0.2,all P<0.05;cholesterol:1.4±0.5 vs 0.9±0.2,0.8±0.2 and 0.5±0.1,all P<0.05)and steatosis(NAFLD activity score:2.4±0.3 vs 1.0±0.2,0.9±0.1 and 0.6±0.1,all P<0.05)in NAFLD mice.In addition,compared with liraglutide or vitamin D group,liraglutide combined with vitamin D treatment was more effective,and might be related to the regulation of insulin resistance and AMPK phosphorylation.Conclusion:The results showed that vitamin D could enhance the therapeutic effect of liraglutide on NAFLD induced by high fat,and may be related to the regulation of insulin resistance and AMPK phosphorylation.

关 键 词：利拉鲁肽 维生素D 非酒精性脂肪肝 小鼠 

分 类 号：R575.5[医药卫生—消化系统]