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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mR-NA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。
Objective To observe the effect of rosiglitazone on AMPKα, GLUT4, IRS1 and peroxisome proliferator activated Receptor γ (PPARγ) expression, provide a scientific basis for the prevention and control of lipotoxicity clinically and effectively. Methods Thirty male Wistar rats were randomly divided into control, high fat and high fat plus rosiglitazone [1 mg / (kg · d)] groups of 10 rats. Five months after feeding, the mRNA levels of AMPKα1, AMPKα2 and GLUT4 in skeletal muscle of rats were determined by Real time PCR. The expressions of IRS1 and PPARγ mRNA were determined by RT-PCR. The expressions of P-AMPK, T-AMPK and GLUT4 Content. Results The mRNA expression of AMPKα2, GLUT4 and PPARγ and the protein levels of P-AMPK, T-AMPK and GLUT4 in high-fat diet group were lower than those in control group except AMPKα1 and IRS1 (P <0.01 or P < 0.05). Rosiglitazone significantly increased the mRNA and protein levels of GLUT4, PPARγ and IRS1, P-AMPK and GLUT4 (P <0.01 or P <0.05) AMPKα2 mRNA levels and T-AMPK protein levels had no significant effect. Conclusion Rosiglitazone can increase the expression of P-AMPK, GLUT4, PPARγ and IRS1 in skeletal muscle of high-fat diet rats, suggesting that Rosiglitazone may be involved in the improvement of insulin resistance and the alleviation of lipotoxicity.