氧化苦参碱对高脂饮食诱导胰岛素抵抗载质蛋白E基因敲除小鼠肝脏三酰甘油代谢酶的影响

Effect of oxymatrine on liver triglyceride metabolism enzymes of apolipoproteinE-/-mice with fatinduced insulin resistance

目的探讨氧化苦参碱对高脂诱导胰岛素抵抗载脂蛋白E基因敲除（ApoE-/-）小鼠肝脏三酰甘油代谢酶的影响。方法72只ApoE-/-小鼠高脂喂养16周，随机分为模型组，氧化苦参碱25 mg/kg、50 mg/kg、100 mg/kg组，灌胃8周，C57BL/6J小鼠设为对照组。测定血清生化指标，高胰岛素-正葡萄糖钳夹试验评价胰岛素抵抗，苏木素伊红（HE）染色观察肝脏病理变化，实时荧光定量聚合酶链反应（QRT-PCR）和免疫印迹分析（Western blot）检测肝组织三酰甘油代谢酶基因表达。结果氧化苦参碱能不同程度降低小鼠体重、血糖、三酰甘油、胆固醇，减轻肝脏病理变化；氧化苦参碱25 mg/kg、50 mg/kg、100 mg/kg组葡萄糖输注率（18.5±1.6）mU·kg-1·min^-1、（20.1±1.8）mU·kg-1·min^-1、（21.3±2.3）mU·kg-1·min^-1，高于模型组（16.5±1.6）mU·kg-1·min^-1（P〈0.05）。与模型组比较，氧化苦参碱组肝脏激素敏感性脂肪酶（HSL）、脂肪三酰甘油酶（ATGL）、过氧化物酶体增殖物激活受体γ（PPARγ）mRNA表达均升高，二酯酰甘油酰基转移酶基因（DGAT1）mRNA表达下降（F＝53.81、21.06、23.67、35.37，均P〈0.05），氧化苦参碱50 mg/kg、100 mg/kg组HSL、ATGL、PPARγ蛋白表达升高，DGAT1蛋白表达下降（F＝53.62、22.87、28.13、33.54，均P〈0.05）。结论氧化苦参碱能改善高脂诱导小鼠的胰岛素抵抗，与调节肝脏三酰甘油代谢酶有关。

ObjectiveTo investigate the effect of oxymatrine on liver triglyceride metabolism enzymes of apolipoprotein E（ApoE）-/-mice with fat-induced insulin resistance.MethodsA total of 72 ApoE-/-mice fed with a high-fat diet for 16 weeks were randomly assigned into a model group, an oxymatrine 25 mg/kg group, an oxymatrine 50 mg/kg group, and an oxymatrine 100 mg/kg group, and oxymatrine was administered p. o.for 8 weeks.C57BL/6J mice were selected to serve as the control group.Serum biochemical parameters were assessed; Insulin resistance was assessed with the Hyper insulinemic-euglycemic clamp test; Pathological changes in the liver were visualized by hematoxylin（HE）staining; levels of gene expression of triglyceride metabolism enzymes were examined by real-time polymerase chain reaction（PCR）and Western-blotting.ResultsAdministration of oxymatrine reduced body weight, fasting blood glucose, cholesterol, and triglyceride to varying degrees and alleviated pathological changes in the liver.Glucose infusion rates were（18.5±1.6）mU·kg-1·min^-1, （20.1±1.8）mU·kg-1·min^-1, and（21.3±2.3）mU·kg-1·min^-1 in the oxymatrine 25, 50, and 100 mg/kg groups, respectively, and were significantly higher than that in the model group（16.5±1.6）mU·kg-1·min^-1（all P〈0.05）. mRNA expression levels of hormone-sensitive lipase（HSL）, adipose triglyceride lipase（ATGL）, and peroxisome proliferator-activated receptor γ（PPARγ）were higher in the three oxymatrine groups than in the model group, while levels of diacylglycerol acyltransferase（DGAT1）were lower in the oxymatrine groups（F=53.81, 21.06, 23.67, 35.37; all P〈0.05）; Levels of HSL, ATGL, and PPARγ were higher, while levels of DGAT1 were lower in the oxymatrine 50 and 100 mg·kg-1 groups than in the model group（F=53.62, 22.87, 28.13, 33.54; all P〈0.05）.ConclusionsOxidative can mitigate insulin resistance in mice fed with a high fat diet through regulating the expression of liver triglyceride metabolism enzymes.