白藜芦醇对链脲菌素所致糖尿病大鼠认知功能障碍的影响

Effects of resveratrol on cognitive dysfunction in streptozotocin- induced diabetic rat model

目的：探讨氯胺酮对白藜芦醇对链脲菌素所致糖尿病大鼠认知功能障碍的影响。方法雄性Wistar大鼠36只，2月龄体重180-220 g，将其随机均分三组（n＝12），对照组（C组）、链脲菌素组（ STZ组）、白藜芦醇组（ RES组）。 STZ组及RES组大鼠腹腔注射60 mg／kg链脲菌素，28 d后分别连续7 d注射等容积生理盐水和100 mg／kg白藜芦醇，于第36 d行Morris水迷宫实验并记录大鼠登台潜伏期及靶象限活动时间比率。随即处死大鼠，取前额皮层测定白介素－1β（IL－1β），白介素－6（IL－6）和AMP依赖的蛋白激酶（ AMPK）含量。结果与C组相比，STZ组大鼠登台潜伏期显著延长且靶象限活动时间缩短，前额皮层IL－1β及IL－6表达显著上调（ P＜0．05）且AMPK显著下调；与STZ组相比，RES组大鼠强迫游泳不动时间显著减少，前额皮层IL－1β及IL－6表达显著下调且AMPK表达显著上调（P＜0．05）。结论白藜芦醇对链脲菌素所致糖尿病大鼠认知功能障碍有显著改善作用，其确切机理可能与前额皮层IL－1β和IL－6下调及AMPK上调有关。

Objective This article was to investigate the effects of resveratrol on cognitive dysfunction in streptozotocin-induced diabetic rat model.Methods Thirty-six male Wistar rats weighing 180-220 g were randomly divided into 3 groups （ n=12 each）：control group （ C group） , streptozotocin group （ STZ group） and resveratrol group （ RES group） .Rats in STZ group and RES group were intraperitoneally injected with 60 mg/kg streptozotocin.Twenty-eight days later, rats were consecutively 7 d administered either saline or 100 mg/kg resveratrol, respectively.Morris water maze was carried out for all the rats to record both the latency to the platform and the proportion of time spent in the target quadrant.Immediately, rats were sacrificed and prefrontal cortex was collected for measuring interleukin-1β（ IL-1β） , interleukin-6 （ IL-6 ） and AMP-activated protein kinase （ AMPK） by using western blot.Results Compared with C group, the latency to the platform prolongated and the proportion of time spent in the target quadrant decreased in rats in STZ group and the expression of IL-1βand IL-6 increased and the expression of BDNF decreased （P〈0.05）.Compared with STZ group, rats in RES group showed significantly shorten in the latency to the platform, the proportion of time spent in the target quadrant prolongated, the expression of IL-1βand IL-6 increased, the expression of AMPK significantly decreased （P〈0.05）.Conclusions Resveratrol has therapeutic effects for streptozotocin-induced cognitive dysfunction, its underlying mechanism is probably related to the decreased expression of IL-1βand IL-6 and increased expression of AMPK in rat prefrontal cortex.