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山东大学学报(医学版)

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罗格列酮对高脂饲养大鼠骨骼肌AMPK活性的影响

孙颖1,2,刘毅3,张捷2,崔彬2,孔磊1,赵家军1
  

  1. (山东大学附属省立医院 1.内分泌科,2.科研中心,3.呼吸内科, 济南 250021)
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2009-03-16 发布日期:2009-03-16
  • 通讯作者: 赵家军

Effects of Rosiglitazone on activities of AMPK
in the skeletal muscle of highfat fed rats

SUN Ying1,2, LIU Yi3, ZHANG Jie2, CUI Bin2, KONG Lei1, ZHAO Jiajun1

  

  1. (1. Department of Endocrinology; 2. Central Laboratory; 3. Department of
    Respiratory, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China)
  • Received:1900-01-01 Revised:1900-01-01 Online:2009-03-16 Published:2009-03-16
  • Contact: ZHAO Jiajun

摘要: 目的观察罗格列酮对高脂饲养大鼠骨骼肌AMP激活的蛋白激酶(AMPK)α、葡萄糖转运体4(GLUT4)、胰岛素受体底物1(IRS1)及过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响,为临床有效的预防和控制脂毒性提供科学依据。方法雄性Wistar大鼠30只,随机分为对照、高脂和高脂加罗格列酮[1?mg/(kg·d)]三组,每组10只。喂养5个月后,采用Real time PCR法测定大鼠骨骼肌中AMPKα1、AMPKα2、GLUT4的mRNA水平,RTPCR法测定IRS1、PPARγmRNA的表达,Western blot法测定PAMPK、TAMPK和GLUT4的含量。结果高脂组大鼠除AMPKα1和IRS1的mRNA表达无变化外,AMPKα2、 GLUT4、PPARγ的mRNA水平及PAMPK、TAMPK、 GLUT4的蛋白水平均比对照组降低(P<0.01或P<0.05)。与高脂组相比,罗格列酮显著增加大鼠骨骼肌GLUT4、PPARγ、IRS1的mRNA水平及 PAMPK、GLUT4的蛋白水平(P<0.01或P<0.05), 而对AMPKα1、AMPKα2的mRNA水平和TAMPK的蛋白水平无明显影响。结论罗格列酮可增加高脂喂养大鼠的骨骼肌PAMPK、GLUT4、PPARγ和IRS1的表达,提示其具有参与改善胰岛素抵抗、缓解脂毒性的作用。

关键词: 罗格列酮, 蛋白激酶,AMP激活, 高脂, 大鼠,Wistar

Abstract: To investigate effects of Rosiglitazone on activities of AMPK (AMPactivated protein kinase),GLUT4 (glucose transport 4),IRS1 (insulin receptor substrate 1), and PPARγ (peroxisome proliferator activated receptor γ) in the skeletal muscle of highfat fed rats. MethodsMale Wistar rats were randomly divided into three groups:the control group (N, n=10), the highfat diet group (HF, n=10), and the Rosiglitazonetreated group (HF+Ros,n=10). After a high fat feeding for four months, rats in the HF+Ros group were treated with Rosiglitazone at a dose of 1?mg/(kg·d) orally for one month. Skeletal muscles of all animals were gained for further analysis. The mRNA levels of AMPKα1, AMPKα2, and GLUT4 were determined using real time PCR and of IRS1 and PPARγ using RTPCR. Protein levels of total AMPK, PAMPK, and GLUT4 were determined by Western blot. ResultsCompared with the controls, the mRNA levels of AMPKα2, GLUT4, and PPARγ were reduced, and also protein expressions of total AMPK, PAMPK and GLUT4 were decreased in rats with a highfat diet. But the AMPKα1 and IRS1 mRNA levels had no changes. Compared with the HF group, Rosiglitazone increased mRNA levels of GLUT4, PPARγ and IRS1 and enhanced protein expressions of PAMPK and GLUT4. But there were no changes in AMPKα1, AMPKα2, and TAMPK. ConclusionRosiglitazone could increase expression of PAMPK, GLUT4, PPARγ, and IRS1 in highfat fed rats, which suggests that it could ameliorate insulin resistance.

Key words: Rosiglitazone, AMPactivated protein kinase, Highfat, Rats,Wistar

中图分类号: 

  • R58
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