目的：本研究主要观察橄榄苦甙（OL）改善肥胖db/db小鼠胰岛素抵抗的作用机制。方法：6-8周龄雄性db/db小鼠12只，按体质量和随机血糖随机分为OL组和模型组，每组6只，另设同周龄C57BL/6J小鼠6只为正常组。OL组灌服OL水溶液50mg·kg^-1体重，其余组给以等剂量生理盐水。治疗4周后，检测各组小鼠的空腹血糖（FBG）、胰岛素水平、计算胰岛素抵抗指数以及口服葡萄糖耐量实验（OGTT），取肝脏组织，采用RT-PCR、Western Blot检测相关基因和蛋白表达。结果：治疗4周后，与模型组比较，OL组体重、空腹血糖、血清胰岛素水平和胰岛素抵抗指数显著降低（P<0.05或P<0.01）；OGTT实验后，OL组血糖明显低于模型组（P<0.01）；OL组小鼠肝脏组织InsR、IRS-1、GLUT-2 mRNA和蛋白表达显著升高（P<0.01）。结论：OL通过提高肝脏InsR、IRS-1、GLUT-2 mRNA和蛋白的表达起到降低血糖、改善胰岛素抵抗的作用。

This study aimed to elucidate the mechanism behind the effects of oleuropein(OL)on improving insulin resistance in obese db/db mice.Twelve 6- to 8-week-old male db/db mice were randomly divided into the model group and the OL group with 6 in each group according to their levels of blood glucose and body weight,while six C57BL/6J mice with the same age were made up for the normal group.Mice of the OL group was intragastrically administered with(50mg·kg^-1)once a day.The mice of the other groups were treated with the saline solution with the same dosage.After treatment for four weeks,OGTT test was carried out,while fast blood glucose and serum insulin were tested. RT-PCT and western blot were used to quantify the mRNA and protein expressions of certain targets in the liver.As a result,it was found that the body weight,fast blood glucose,serum insulin level and insulin resistance index were significantly decreased in the mice of the OL group when compared with model group after the treatment for 4 weeks(P<0.05 or P<0.01).Plasma glucose levels at each time point of OGTT tests were lower in the mice of the OL group than those of the model group(P<0.01).The mRNA and protein expressions of InsR,IRS-1 and GLUT-2 in the mice of the OL group increased significantly(P<0.01).In conclusion,it was demonstrated that oleuropein may reduce the blood glucose and improve the insulin resistance in db/db mice through up-regulating the mRNA and protein expressions of InsR,IRS-1 and GLUT-2 in the liver.

北京市教育委员会科学研究与研究生培养共建项目—科研项目：中药干预胰岛素抵抗技术平台建设与方药筛选研究，负责人：刘铜华。