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目的研究自发性Zucker fa/fa(ZF)大鼠评价胰岛素增敏剂药效时需要注意的问题,确定入组标准、检测指标、评价标准。方法20只雄性ZF大鼠按照体质量均一原则分为模型对照组和罗格列酮组(每组10只),10只Zucker fa/?大鼠设为正常对照组。罗格列酮组以胰岛素增敏剂罗格列酮作为阳性药物,6mg/kg灌胃给药;模型对照组和正常对照组给予水。结果罗格列酮能明显降低大鼠的血清胰岛素、甘油三酯及游离脂肪酸水平(P<0.05);高胰岛素-正常血糖钳夹实验结果表明,能明显提高罗格列酮组大鼠的葡萄糖输注率与胰岛素敏感指数(P<0.05)。胰腺病理组织学检查表明罗格列酮能缓解大鼠胰岛细胞的增生肥大。结论以ZF大鼠模型评价胰岛素增敏剂药效时,选用7～8周龄自发性ZF雄性大鼠,以空腹胰岛素水平高于4ng/ml为纳入标准,以甘油三酯、游离脂肪酸及血清胰岛素水平与高胰岛素-正常血糖钳夹实验结果为评价指标,由此方法建立的动物模型可用于评价胰岛素增敏剂的药效作用。
Objective To study the problems that need attention in spontaneous Zucker fa / fa (ZF) rats to evaluate the efficacy of insulin sensitizer, and to determine the inclusion criteria, test indexes and evaluation criteria. Methods Twenty male ZF rats were divided into model control group and rosiglitazone group (n = 10) according to the principle of uniform body weight. Ten Zucker fa rats were used as normal control group. Rosiglitazone group with insulin sensitizer rosiglitazone as a positive drug, 6mg / kg intragastric administration; model control group and the normal control group given water. Results Rosiglitazone significantly decreased the level of serum insulin, triglyceride and free fatty acid in rats (P <0.05). The results of hyperinsulinemic-normal glucose clamp showed that the glucose Infusion rate and insulin sensitivity index (P <0.05). Pancreatic histopathological examination showed that rosiglitazone can relieve the proliferation and hypertrophy of islet cells in rats. Conclusion ZF rat model to evaluate the efficacy of insulin sensitizer, the selection of 7 to 8 weeks of spontaneous ZF male rats to fasting insulin levels higher than 4ng / ml for the inclusion criteria, triglycerides, free fatty acids and serum Insulin levels and high insulin-normal blood glucose clamp experimental results for the evaluation of indicators, animal models established by this method can be used to evaluate the efficacy of insulin sensitizers.