尼克酰胺核糖对肝脏胰岛素抵抗的影响  

Effect of nicotinamide riboside on insulin resistance in mice liver

作　　者：马思晰 黎秋燕 高梦琦 肖颖 谷莹莹 庞能智 杨丽丽[1] MA Sixi;LI Qiuyan;GAO Mengqi;XIAO Ying;GU Yingying;PANG Nengzhi;YANG Lili(Department of Nutrition,School of Public Health,Sun Yat-sen University,Guangzhou,Guangdong 510080,China)

机构地区：[1]中山大学公共卫生学院营养与食品卫生学系,广东广州510080

出　　处：《热带医学杂志》2024年第4期460-464,F0004,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81872613)。

摘　　要：目的探究尼克酰胺核糖(NR)能否改善肝脏胰岛素抵抗。方法将C57BL/6J小鼠随机分为对照组(n=8)、模型组(n=8)、NR干预组(NR组,n=7)。对照组喂养标准对照饲料(XT304),每天进行双蒸水灌胃;模型组和NR干预组给予高果糖高脂饲料(XT310,40%碳水化合物,40%脂肪),模型组每天进行蒸馏水灌胃,NR组每天给予400 mg/(kg·BW)NR溶液灌胃干预。饲养11周采用糖耐量实验、空腹胰岛素检测实验、肝脏切片染色观察。用0.25 mmol/L棕榈酸(PA)干预HepG2细胞24 h,建立胰岛素抵抗模型,添加0.5 mmol/L NR同时干预。干预结束后,给予100 nmol/L胰岛素刺激HepG2细胞30 min后进行糖摄取检测。进一步检测线粒体活性。结果终止实验时,各组小鼠体重分别为对照组(28.60±0.72)g、模型组(27.00±1.98)g、NR组(23.44±1.89)g,差异有统计学意义(F=33.540,P<0.05),NR组有体重降低的趋势。与对照组的糖耐量曲线下面积(1167.56±91.15)比较,模型组的糖耐量曲线下面积(1579.25±313.21)明显升高,NR组糖耐量曲线下面积(1334.25±102.00)较模型组明显降低,差异有统计学意义(F=7.003,P<0.05)。3组的胰岛素水平、胰岛素抵抗指数变化趋势与糖耐量实验一致(P<0.05)。肝脏组织切片HE染色显示,与模型组相比,NR组肝脏脂质蓄积减少。细胞实验表明,与PA组相比,NR组HepG2细胞糖摄取能力减弱。PA干预后,肝细胞线粒体活性相对于空白组明显降低,而NR可以改善PA诱导的肝细胞线粒体活性降低(F=31.480,P<0.05)。结论NR可以改善肝脏胰岛素抵抗,其机制可能与线粒体有关。Objective To explore whether nicotinamide ribose(NR)can improve hepatic insulin resistance.Methods C57BL/6J mice were randomly divided into control group(n=8),model group(n=8),and NR intervention group(NR group,n=7).The control group was fed with the standard control diet(XT 304)with double steam gavage daily;the model group and nicotinamide ribose intervention group were given high fructose and high fat diet(XT 310,40%carbohydrate,40%fat),the model group received distilled gavage daily and the NR group received 400 mg/(kg·BW daily)NR solution gavage intervention.The whole animal experiment proceeded for 11 weeks.Oral glucose tolerance test(OGTT)and fasting insulin test were used to evaluate the glucose regulation ability of mice.Liver hematoxylin and eosin staining sections were used to verify whether hepatic lipid accumulation could be alleviated by NR.HepG2 cells were intervened with 0.25 mmol/L palmitic acid(PA)for 24 h to establish an insulin resistance model,and 0.5 mmol/L NR was added for intervention.At the end of the intervention,100 nmol/L insulin was given to stimulate HepG2 cells for 30 minutes and then glucose uptake assay was performed.Mitotracker Red staining was used to preliminarily explore the mechanism of NR in preventing hepatic insulin resistance.Results At the termination of the experiment,the body weights of mice in each group were as follows:control group(28.60±0.72)g,model group(27.00±1.98)g,and NR group(23.44±1.89)g.Comparison of the body weights of the three groups of mice showed that there was a trend of lower body weight in the NR group,and the difference was statistically significant(F=33.540,P<0.05).There was a significant difference in the area under the glucose tolerance curve among the three groups(F=7.003,P<0.05),and the area under the glucose tolerance curve in the model group(1579.25±313.21)was significantly higher(P<0.05)compared with that in the control group(1167.56±91.15).The area of the glucose tolerance curve was significantly lower in the NR group(1334.25±102.00)

关 键 词：尼克酰胺核糖 肝脏 胰岛素抵抗 HEPG2细胞 

分 类 号：R587.1[医药卫生—内分泌]