吡格列酮对AD大鼠模型学习记忆及GSK-3β、p-tau蛋白的影响  

Effect of Pioglitazone on the learning memory and glycogen synthase kinase 3 and hyperphosphorylated tau protein in model of AD rates

作　　者：白娟[1] 张生林[1] 杨宁宁[1] 李海洋[1] 马君[2] 

机构地区：[1]山西医科大学第一临床医学院老年病科,太原030001 [2]武警山西总队医院,太原030006

出　　处：《中国医疗前沿》2010年第21期28-29,43,共3页China Healthcare Innovation

摘　　要：目的观察吡格列酮对阿尔茨海默病(AD)大鼠模型学习记忆能力及海马糖原合成激酶3-β(GSK-3β)活性、tau蛋白异常磷酸化(p-tau)的影响,为临床防治AD提供一条新的思路。方法健康雄性Wistar大鼠32只,随机分为4组,除对照组外其余组大鼠海马CA1区注射冈田酸(OA)制备AD模型;低、高吡格列酮组给予吡格列酮灌胃4周,其余组给生理盐水灌胃;通过水迷宫检测各组大鼠学习记忆能力;免疫组化法观察各组大鼠海马GSK-3β活性、tau蛋白异常磷酸化。结果与对照组相比,模型组学习记忆能力明显下降(P<0.05),海马GSK-3β、tau蛋白磷酸化的表达明显增多(P<0.05);与模型组相比,低、高吡格列酮组学习记忆能力明显提高(P<0.05),海马GSK-3β、tau蛋白磷酸化的表达明显减少(P<0.05),而低、高吡格列酮组二者相比无明显差异(P>0.05)。结论吡格列酮可改善AD大鼠模型学习记忆能力,可能与降低GSK-3β活性、减少tau蛋白过度磷酸化有关。Objective To investigate the effects of Pioglitazone on the learning memory and glycogen synthase kinase 3 and hyperphosphorylated tau protein in modle of AD rates, for the prevention and treatment of Alzheimer＇s disease and provide a new way of thinking. Methods To selecte male normal rats that was randomly divided into four groups. Except the control group, other groups was injected with okadaic acid（OA） to make AD models. Low and high Pioglitazone group was given Pioglitazone for 4 weeks, other groups were given NS. Morris test was used to determine the ability of learning and memory. Immunohistochemical method to observe the hippocampal GSK-3βand tau protein expression of phoshorylated. Results Compared with the control group, model group was significantly decreased the ability learning and memory（P0.05）, hippocampal GSK-3β and tau phosphorylation was significantly increased（P0.05）; Compared with model group, low and high Pioglitazone group was significantly improved the ability learning and memory（P0.05）, hippocampal GSK-3β and tau phosphorylation was significantly reduced（P0.05）, but there was no significant difference between low and high Pioglitazone group（P0.05）. Conclusion Pioglitazone can improve the learning and memory ability of AD rats, it may reduce the activity of GSK-3β, reducing tau protein phosphorylation.

关 键 词：吡格列酮 阿尔茨海默病 GSK-3Β p-tau蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]