目的:探讨熊果酸(UA)改善自发性2型糖尿病KKAy小鼠胰岛素抵抗的作用和机制。方法:KKAy小鼠35只,根据随机区组设计方法,分为糖尿病对照组、罗格列酮组、非诺贝特组、熊果酸高剂量组和熊果酸低剂量组,每组7只,以C57BL/6J小鼠作为正常组。药物干预4周,进行一般状态观察,口服糖耐量检测,计算胰岛素抵抗指数(HOMA-IR),采用免疫组化法检测葡萄糖转运体(GLUT4)的表达,并用Westen-blot法进一步检测小鼠肌细胞膜GLUT4蛋白转运情况。结果:与糖尿病对照组相比,熊果酸高剂量组小鼠糖耐量和胰岛素抵抗指数明显改善(P〈0.01);熊果酸对小鼠肌细胞GLUT4蛋白表达和转运的影响与对照组比较差异有统计学意义(P〈0.01)。结论:熊果酸可有效改善自发性2型糖尿病KKAy小鼠糖耐量和胰岛素抵抗指数,可能是通过提高小鼠肌细胞GLUT4蛋白转运和表达来实现的。
Objective: To explore the effects and mechanism of Ursolic acid(UA) improving insulin resistance in spontaneous type 2 diabetes, the KKAy mice. Methods: 35 KKAy mice were divided into 5 groups according to randomized block design, which were control group, rosiglitazone group, fenoflbrate group, UA high-dose group and UA low-dose group respectively, with C57BL/6J mice as normal control group, 7 mice per group. In the meantime, the influence of mice ordinary condition, oral glucose tolerance test(OGTT) and HOMA-IR was detested. At the end of the 4th week, the protein expression of glucose transporter 4(GLUT4) and the transport situation were detected by immunohistochemisty method and western blot respectively. Results: After 4 weeks intervention, OGTT and HOMA-IR in high dose Ursolic acid group have changed, showing statistically significant differences compared to DM control group(P〈0.01); high dose Ursolic acid has depressant effect on the GLUT4 protein expression and transshipment(P〈0.01). Conclusion: The effects of UA in improving spontaneous T2DM KKAy mice insulin resistance might be closely related with affecting content of GLUT4 and regulating the transshipment of GLUT4.