以自发性大鼠模型-第三军医大学学报.DOC

以自发性大鼠模型评价胰岛素增敏剂药效时几个问题的初步探讨作者简介 作者简介：王晓琳，女，重庆市人，博士研究生，主要从事糖尿病动物模型方面的研究工作。电话：（023 E-mail：sabrina3@ 通信作者：邱宗荫，电话：（023E-mail：zongyin141@126.com 收稿日期：2009-3-31 修回日期： 王晓琳1，邱宗荫1，夏永鹏2（1 重庆医科大学：药学院，重庆 400016；2 重庆食品药品监督管理局：，重庆 400042） 摘 要 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 雄性ZF大鼠分为模型对照组和给药组；给药组以胰岛素增敏剂罗格列酮作为阳性药物，6 mg/kg灌胃给药；对照组给予水。结果 罗格列酮能明显降低给药组大鼠的血清胰岛素、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，能提高给药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给药组大鼠的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4 ng/mlml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。 关键词：Zucker fa/fa大鼠；罗格列酮；高胰岛素-正常血糖钳夹实验；胰岛素敏感性 中图法分类号： 文献标识码： Discuss Some Points in Evaluating Effects of Insulin Sensitizer with Spontaneous Rat Model Wang Xiaolin1, Qiu Zongyin1, Xia Yongpeng2 （1 Pharmaceutical Institute，Chongqing Medicinal University，Chongqing 400016; 2 Chongqing Food and Drug Administration，Chongqing 400042，China） Abstract: Objective The study was aimed at discussing some points in evaluating effects of insulin sensitizer with Zuker fa/fa rat model, including entrance standard and evaluation standard. Methods Male Zucker fa/fa rats were divided into two groups, one group were fed Rosiglitazone at 6 mg/kg and the other were fed water as control. Results Rosiglitazone could reduce levels of fasting insulin, triglyceride（TG） and free fatty acid（FFA）of Zuker fa/fa rats（P＜0.05）, increase glucose infusion rate（GIR） and insulin sensitive index（ISI） of Zuker fa/fa rats in hyperinsulinemic-euglycemic clamps（P＜0.05）. The result of the hematoxylin and eosin（HE） dyeing demonstrated that Rosiglitazone had significantly improved the hypertrophy and hyperplasia of the islets of Langerhans. Conclusion In order to evaluating effects of insulin sensitizer with Zuker fa/fa rat model, it should choose Zucker fa/fa rats （7 or 8-week-old and level of fasting insulin over 4 ng/mLml） by inspecting levels of fasting insulin, TG