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

doi:10.12047/j.cjap.5911.2020.057

摘要/Abstract

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。

关键词: 利拉鲁肽, 维生素D, 非酒精性脂肪肝, 小鼠

Abstract: 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.

Key words: liraglutide, vitamin D, nonalcoholic fatty liver, mice

中图分类号:

R575.5

王锋, 张海峰. 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[J]. 中国应用生理学杂志, 2020, 36(3): 261-264.

WANG Feng, ZHANG Hai-feng. Effects of liraglutide combined with vitamin D on non-alcoholic fatty liver induced by high fat in mice and its mechanism[J]. CJAP, 2020, 36(3): 261-264.

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