氧化苦参碱改善高脂诱导ApoE^(-/-)小鼠的胰岛素抵抗  

Oxymatrine ameliorates high fat-induced insulin resistance in ApoE^(-/-) mice

作　　者：王超[1] 张会欣 邢邯英[1] 王杏[1] 张哲[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,河北石家庄050051 [2]河北以岭医药研究院药理室,河北石家庄050035

出　　处：《中国病理生理杂志》2016年第11期2010-2014,共5页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究发展计划(973计划)项目(No.2012CB518606);河北省重大医学科研项目(No.zd2013002;No.zd2013004)

摘　　要：目的:观察氧化苦参碱对高脂诱导胰岛素抵抗小鼠的作用并初步探讨可能机制。方法:Apo E^(-/-)小鼠高脂喂养16周,分为胰岛素抵抗组以及氧化苦参碱25、50、100 mg/kg组,C57BL/6J小鼠设为对照组,每组10只。灌胃给药8周后,进行小鼠葡萄糖耐量实验;测定血清空腹血糖(FBG)、甘油三酯(TG)、胆固醇(TC)、游离脂肪酸(FFA)和空腹胰岛素(FINS)的含量;实时荧光定量PCR测定肝组织胰岛素受体(INSR)、胰岛素受体底物-2(IRS-2)和葡萄糖转运子2(GLUT_2)的mRNA表达;Western blot法测定肝组织GLUT_2、INSR、IRS-2、p-INSR、p-IRS-2、磷脂酰肌醇3-激酶(PI3K)、p-PI3K、丝氨酸/苏氨酸蛋白激酶(AKT)和p-AKT的蛋白水平。结果:氧化苦参碱能不同程度降低FBG、TG、TC、FFA和FINS水平,改善胰岛素抵抗;氧化苦参碱组INSR、IRS-2和GLUT_2的mRNA表达比胰岛素抵抗组升高(P<0.05),p-INSR/INSR、p-IRS-2/IRS-2、p-PI3K/PI3K、p-AKT/AKT和GLUT_2的蛋白水平也升高(P<0.05)。结论:氧化苦参碱能通过PI3K/AKT通路,改善高脂诱导小鼠的胰岛素抵抗。AIM： To investigate the effect of oxymatrine（ OXY） on high fat-induced insulin resistance in mice,and to investigate the mechanism. METHODS： Apo E^-/-mice with high-fat diet for 16 weeks were divided into insulin resistance group,and OXY groups at concentrations of 25,50 and 100 mg / kg. C57 BL /6J mice served as normal control group. The mice in OXY groups were gavaged with OXY for 8 weeks. Glucose tolerance test in the mice was performed. Fasting blood glucose（ FBG）,total cholesterol（ TC）,triglyceride（ TG）,fatty acid（ FFA） and fasting insulin（ FINS） in the plasma were measured. The mRNA expression of insulin receptor（ INSR）,insulin receptor substrate-2（ IRS-2）,glucose transporter 2（ GLUT2） in the liver tissues was examined by RT-q PCR. The protein levels of GLUT2,INSR,IRS-2,p-INSR,p-IRS-2,PI3 K,p-PI3 K,serine / threonine protein kinase（ AKT） and p-AKT were examined by Western blot. RESULTS： OXY reduced the levels of FBG,TC,TG,FFA and FINS,and attenuated insulin resistance.Compared with insulin resistance group,the mRNA expression of INSR,IRS-2 and GLUT2 significantly increased in OXY groups（ P〈0. 05）. The protein levels of p-INSR / INSR,p-IRS-2 / IRS-2,p-PI3 K / PI3 K,p-AKT / AKT and GLUT2 also increased in OXY groups（ P〈0. 05）. CONCLUSION： OXY ameliorates high fat-induced insulin resistance in mice via PI3 K / AKT pathway.

关 键 词：氧化苦参碱 高脂饮食 胰岛素抵抗 胰岛素 PI3K/AKT信号通路 

分 类 号：R587.1[医药卫生—内分泌] R363[医药卫生—内科学]