摘要
目的:观察雌激素对阿尔茨海默病(AD)大鼠学习记忆及海马神经元损伤的影响,探讨雌激素神经保护的机制。方法:选取雌性成年SD大鼠24只,随机分为对照组、AD+雌二醇(E2)组、AD组,每组8只。Morris水迷宫检测大鼠学习记忆功能,苏木精-伊红(H-E)染色及Bielschowski染色法观察海马神经元形态,免疫组化法观察Tau蛋白异常磷酸化变化及GSK-3β活性。结果:与AD组相比,AD+E2组大鼠迷宫测试明显改善(P<0.01);海马CA1区神经元纤维形态规则,Tau蛋白磷酸化阳性细胞数明显减少(P<0.01),Tau蛋白表达减少,且GSK-3β总量及磷酸化GSK-3β含量均有所增加。结论:雌激素治疗可改善Aβ诱导的大鼠学习记忆障碍及海马神经元损伤,可能通过作用GSK-3β导致Tau蛋白去磷酸化,从而达到保护神经的目的。
Objective： To study the effects of estrogen on the impairment to learning memory and hippocampus neurons in rats with Alzheimer＇s disease（AD）,and to explore its mechanism of neuroprotection.Methods： Twenty-four female rats were equally randomized into a normal control,an AD＋E2 and an AD group.The performance of learning memory was tested by Morris water maze,the tau hyperphosphorylation and the activity of GSK-3β detected by immunohistochemical staining,and the pathological changes of hippocampus observed by H-E and Bielschowski staining.Results： Compared with the AD group,results showed a significant improvement in the performance of learning memory（P〈0.01）,regular morphology of the neurofibrils in the hippocampus,a remarkable decrease in the number of P-Tau positive cells（P〈0.01）,as well as in the total amount of GSK-3β and the content of phosphorylation of GSK-3βand Tau protein in the hippocampus.Conclusion： Estrogen can improve Aβ-induced impairment to learning memory and hippocampus neurons in AD rats.The neuroprotection mechanism of estrogen may be involved in its dephosphorylation of the Tau protein by alteration of GSK-3β.
出处
《医学研究生学报》
CAS
2008年第10期1040-1043,I0002,共5页
Journal of Medical Postgraduates
基金
南京军区南京总医院科研基金资助项目(批准号:2006024)
