吡格列酮改善脑室注射链脲霉素诱导的小鼠认知损害及其机制的研究  

Pioglitazone attenuates cognitive impairment induced by intracerebroventricular streptozotocin injection in mice and underlying mechanisms

作　　者：汪魏平[1] 唐苏苏[2] 徐文科[1] 张亭亭[2] 汪平君[1] 洪浩[2] 

机构地区：[1]皖南医学院弋矶山医院药剂科 [2]中国药科大学药理教研室

出　　处：《中国临床药理学与治疗学》2011年第9期986-991,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:研究吡格列酮对脑室注射链脲霉素诱导小鼠认知损害的影响及其作用机制。方法:采用双侧脑室注射链脲霉素(0.5 mg/kg)制备小鼠认知损害模型,吡格列酮连续灌胃给药20 d,每天1次,采用Morris水迷宫和Y迷宫试验评价认知功能,并测定脑内乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(ChAT)以及外周血糖水平。结果:吡格列酮(9 mg.kg-1.d-1,18 mg.kg-1.d-1)能显著缩短小鼠在可见平台试验中寻找平台的潜伏期,增加空间探索试验中平台所在象限停留时间百分率;增加Y迷宫测试中的正确反应次数。吡格列酮还能显著增加小鼠脑组织海马区和皮层区Ach含量,降低AchE活性,并且增加ChAT活性,但对动物外周血糖无明显影响。结论:吡格列酮可通过降低AchE活性和提高ChAT活性,使小鼠脑内Ach含量增加,从而改善脑室注射链脲霉素所致的小鼠认知损害。AIM： To investigate the effects of pioglitazone on the cognitive impairment induced by intracerebroventricular streptozotocin injection in mice and underlying mechanisms.METHODS： Streptozotocin（0.5 mg/kg） was intracerebroventricularly injected to induce cognitive impairment in mice.Pioglitazone was administered through a gastric tube every day for consecutive 20 days.The cognition function was evaluated by Morris water maze test and Y maze test.The Ach,AchE and ChAT of the hippocampus and cortex,and the blood glucose level in mice were determined.RESULTS：Pioglitazone（9 mg·kg-1·d-1,18 mg·kg-1·d-1） significantly decreased the escape latency in visible platform test,increased the time spent in the platform quadrant in the spatial probe test,and significantly increased the correct number in Y maze test.Pioglitazone also significantly increased Ach levels and ChAT activity,and decreased AchE activity in hippocampus and cortex of mice.The difference in the level of blood glucose was not observed among groups.CONCLUSION： Pioglitazone may improve the cognition impairment induced by intracerebroventricular streptozotocin injection through the elevation of Ach levels that results from the decreased activity of AchE and increased activity of ChAT.

关 键 词：吡格列酮 链脲霉素 认知损害 乙酰胆碱 乙酰胆碱酯酶 乙酰胆碱转移酶 

分 类 号：R965.1[医药卫生—药理学]