目的 观察胰岛素抵抗大鼠认知行为及海马阿尔茨海默病(Alzheimer disease， AD)样病理改变，研究罗格列酮(rosiglitazone，RSG)对其认知及AD样病变的干预作用及可能的机制。方法 建立胰岛素抵抗大鼠模型，将成模的20只大鼠随机分为胰岛素抵抗(insulin resistance，IR)组和罗格列酮(RSG)组，每组10只，未造模的正常大鼠作为对照(CTL)组(n=10)。RSG组予高脂高糖高蛋白饮食+罗格列酮片3.0 mg/(kg·d)灌胃4周;IR组予高脂高糖高蛋白饮食+等量生理盐水灌胃4周;CTL组予普通饮食+等量生理盐水灌胃4周。观察指标为各组大鼠血糖、血浆胰岛素水平、胰岛素抵抗指数(IRI)、水迷宫行为能力测定、海马中IDE、pAKT、Aβ蛋白表达。结果 IR组与RSG组胰岛素抵抗指数(8.56±0.43和3.82±0.38)较CTL组(2.27±0.25)高，而RSG组低于IR组。IR组和RSG组大鼠第4天逃避潜伏期[(63.21±5.67)s和(37.48±5.41)s]较CTL组[(24.14±5.49)s]明显延长;IR组和RSG组穿越原平台象限时间占总时间百分比[(21.88±3.85)%和(33.43±2.98)% ]较CTL组[(39.57±4.31)%]减小，而RSG组较IR组明显延长。IR组和RSG组Aβ40蛋白阳性表达(0.27±0.023和0.56±0.011)较CTL组(0.13±0.021)强，而RSG组较IR组弱。上述差异均有统计学意义(P＜0.01或P＜0.05)。结论 胰岛素抵抗大鼠认知行为明显下降，罗格列酮可改善其认知行为，减轻Aβ在海马的沉积。其机制可能与通过胰岛素通路PI3K/AKT介导的IDE上调，增强IDE对Aβ的降解相关。

Objective To study the insulin resistance rat cognitive behavior and hippocampal Alzheimer disease (AD) - like pathological change, to study the intervention effect of rosiglitazone (RSG) on the cognitive and AD- like lesions and its possible mechanism. Methods The rat models of insulin resistance were established and 20 successful models were randomly divided into the insulin resistance(IR)group(n=10) and rosiglitazone (RSG) group, each group of 10,the normal rats as control (CTL)group(n=10).The rats in RSG group were given high-protein diet with high fat and sugar +RSG 3 mg/kg/d by gavage for 4 weeks. IR group were given high-protein diet with high fat and sugar + equivalent saline by gavage for 4 weeks.CTL group were given general diet + equivalent saline by gavage for 4 weeks. The observation indexes included the blood glucose,plasma insulin levels(FINS),insulin resistance index(IRI),Morris water maze test,insulin degrading enzyme (IDE),response to insulin sialing pathway of pAKT,and Aβ protein expression in hippocampus. Results The IRI in IR group and RSG group(8.56±0.43 and 3.82±0.38)is low than that in CTL group(2.27±0.25),but in RSG group was lower than in IR group. The 4 day escape latency of rats in IR and RSG groups[(63.21±5.67)s and(37.48±5.41)s] was significantly longer than in CTL group [(24.14±5.49)s].The through the platform quadrant percentage of total time in IR and RSG groups [(21.88±3.85)% and (33.43±2.98)%] was smaller than in CTL group [(39.57±4.31)%],but RSG group is superior to IR group. The Aβ protein expressions in IR group and RSG groups (0.27±0.023 and 0.56±0.011)was stronger than that in CTL group(0.13±0.021), but RSG group is weaker than IR group. These differences were statistically significant (P<0.01 or P<0.05). Conclusions Insulin resistance rats can develop cognitive behavior decrease and aβ deposition AD like pathological changes.RSG can improve the cognitive behavior, reduce the aβ in the hippocampus of deposition, its mechanism may be through the insulin pathway mediated by IDE PI3K/AKT,to enhance IDE of aβ, thereby reducing degradation deposition.