异黄酮苷元防治AD及抑制Aβ神经毒作用的分子机制研究

被引：0

作者：

杨红

机构：

[1] 暨南大学

关键词：

异黄酮苷元; 阿尔茨海默病; Aβ神经毒性; PKC信号通路;

D O I：

暂无

年度学位：

2010

学位类型：

博士

导师：

周天鸿;

摘要：

本文研究异黄酮苷元防治阿尔茨海默病(AD)的作用及其抑制Aβ神经毒性发挥神经保护作用的分子机制。以脱脂豆粕为原料,筛选优化酸水解转化异黄酮活性苷元的制备工艺；利用H2O2和Aβ25-35诱导的PC12细胞损伤模型和SAM/P8系AD小鼠模型,通过避暗实验和Y-迷宫实验测试AD小鼠学习与记忆能力,通过测定LDH酶、SOD酶、GSH-Px酶的活力和MDA水平,检测PC12细胞和AD小鼠的抗氧化能力；通过测定海马神经组织β-分泌酶活性和大脑皮层胆碱酯酶(AchE)活性,检测Aβ的形成和Ach的降解及神经细胞形态的变化；通过测定PKC活性和对α、β-分泌酶活性的调节及拮抗剂(Myr)的阻断作用,研究异黄酮苷元抑制Aβ神经毒性的信号转导途径。研究结果显示,本制备工艺可获得高活性、高纯度的异黄酮苷元(含量为70.98%),该组分显著提高AD小鼠的学习记忆能力和抗氧化能力,并上调α-分泌酶活性和下调β-分泌酶及AchE酶活性,减少Aβ形成和Ach降解,有效保护神经细胞的形态和功能。本研究从细胞水平和动物水平阐明了异黄酮苷元防治AD的作用,并探讨了其通过激活PKC快速信号转导通路调节α、β-分泌酶活性,从而抑制Aβ形成及其神经毒性发挥神经保护作用的分子机制,为异黄酮苷元用于AD治疗提供科学依据。

引用

页数：101

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