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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

锌螯合剂HQ-O对APP-PS1小鼠和患有阿尔茨海默病的人类组织切片中淀粉样斑块的高对比度和高分辨率标记：实际和理论上的考虑

卷 16, 期 7, 2019

页: [577 - 586] 页: 10

弟呕挨: 10.2174/1567205016666190725155038

open access plus

摘要

背景：在许多有关阿尔茨海默氏病的研究中，已经采用了各种方法来定位淀粉样斑块。 这些斑块中的大多数被认为是由于斑块对聚集的Aβ的亲和力而标记了斑块。 然而，已知斑块包含许多其他成分，包括诸如锌的多价金属。 目的：研究是否可以在患病的大脑的实质和血管淀粉样斑块中定位锌的存在。 为此，研究了一种新型荧光锌螯合剂HQO，及其在淀粉样斑块高对比度和高分辨组织学定位中的作用机制，并对其染色进行了优化。 方法：开发了一种新型的锌螯合剂HQ-O，用于在淀粉样斑块中定位锌。 组织学包括将组织切片在HQ-O的稀水溶液中孵育。描述了其与多种其他荧光方法的兼容性。 结果：所有淀粉样蛋白斑块均被细微染色，在蓝光激发下呈亮绿色。 实质斑块的染色与抗Aβ抗体染色后的染色密切相关，但是，HQ-O有时还会标记血管内的其他球状结构。原位机理研究表明，只有在锌存在下合成Aβx-42聚集时，HQ-O才能观察到荧光斑块状结构。 结论：锌与所有淀粉样蛋白斑块紧密结合，使用新型荧光锌螯合剂HQ-O的组织学定位证明了锌的存在。 另外，示踪剂由于其高锌含量也能够标记血管内白细胞。

关键词: 淀粉样斑块，阿尔茨海默病，锌螯合剂，脑病理学，Aβ，淀粉酶。

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