别嘌呤醇改善高果糖诱导的大鼠胰岛素抵抗的实验研究

Experimental study of allopurinol on insulin resistance in high-fructose rats

目的研究别嘌呤醇对高果糖诱导的胰岛素抵抗性的影响。方法 Wistar雄性大鼠随机分为正常组、模型组和实验组。实验组和模型组,以高果糖饲料喂养同时用别嘌呤醇(25μg·g^(-1))或等量双蒸水灌胃4周。用口服葡萄糖耐量实验法和高胰岛素-正常葡萄糖钳夹法,研究别嘌呤醇对胰岛素敏感性的作用,测定各组空腹血糖、空腹胰岛素水平和血清尿酸水平的变化。结果血清尿酸水平,与正常组的(1.33±0.12)mg·d L^(-1)相比,模型组(1.82±0.10)mg·d L^(-1)明显增高(P<0.05);与模型组相比,实验组(0.90±0.27)mg·d L^(-1)能明显改善由高果糖引起的尿酸浓度的增高(P<0.05)。不同时间段各组之间血糖值无明显差异。模型组的胰岛素敏感性指标(GIR)明显低于正常组(P<0.05),表明出现胰岛素抵抗性;实验组的GIR值明显高于模型组(P<0.05)。结论别嘌呤醇可以提高骨骼肌胰岛素敏感性,明显改善高果糖诱导的胰岛素抵抗性。

Objective To investigate allopurinol（ a xanthine oxidase inhibitor） improves insulin resistance of rats fed with high- fructose diet.Methods Male Wistar rats were randomly divided into 3 groups and each group was fed one of the following diets for 4 weeks： standard chow diet（ normal group）,high- fructose diet（ model group）,and high-fructose diet plus allopurinol（ allopurinol 25 μg·g^-1,test group）. Insulin sensitivity index was assessed from the oral glucose tolerance test（ OGTT） and the euglycemic clamp studies. Results Serum uric acid and plasma insulin concentrations were significantly decreased with allopurinol treatment. That the serum uric acid of the model group with（ 1. 82 ± 0. 10） mg·d L^-1was significantly increased than normal group with（ 1. 33 ± 0. 12） mg · d L^-1,and improved by test group with（ 0. 90 ± 0. 27） mg·d L^-1. There was no difference in the levels of glucose with OGTT among the 3 groups. The model group produced a marked decrease in insulin sensitivity index（ GIR） compared with normal group（ P〈0. 05）. Allopurinol treated high- fructose fed rats showed a significant increase in GIR,reaching a similar level as that of the normal group（ P〈0. 05）. Conclusion Allopurinol may improve of insulin resistance in high- fructose induced insulin resistant.