锌离子与锌转运体6在APP/PS1转基因小鼠小脑内的分布  

Distribution of zinc ions and zinc transporter-6 in the APP/PS1 transgenic mouse cerebellum

作　　者：张丽红[1] 于丹[1] 王辛[1] 郑玮[1] 荣明[1] 王占友[1] 

机构地区：[1]中国医科大学基础医学院组织胚胎学教研室,辽宁沈阳110001

出　　处：《复旦学报（医学版）》2009年第1期65-69,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(30670722;30770680);高等学校博士学科点专项科研基金项目(20060159001)

摘　　要：目的研究游离锌离子和锌转运体6(zinc transporter 6,ZnT6)在APP/PS1转基因小鼠小脑内的分布。方法应用浸入式金属自显影技术(AMG)和免疫组织化学染色标记游离锌离子、ZnT6和淀粉样前体蛋白(amyloid precursor protein,APP),通过免疫荧光染色和共聚焦激光扫描显微镜观察ZnT6和β-淀粉样蛋白(β-amyloid,Aβ)在老年斑内的定位,并分析锌离子、ZnT6与APP和Aβ分布的相关性。结果游离锌离子、ZnT6和APP免疫阳性反应产物均定位于老年斑内,老年斑主要分布于小脑分子层,浦肯野细胞层和颗粒层分布较少;ZnT6和Aβ荧光双标的结果进一步证实两者共存于老年斑内。结论APP/PS1转基因小鼠小脑Aβ老年斑内有大量的ZnT6蛋白表达,并聚集着大量的锌离子,提示锌离子可能参与小脑Aβ老年斑的形成,而ZnT6在老年斑内锌离子的聚集过程中起着重要的调节作用。Objective To investigate the distribution of free zinc ions and zinc transporter-6 （ZnT6） in the APP/PS1 transgenic mouse cerebellum. Methods Immersion autometallography （AMG） and immunohistochemistry were used to analyze the distribution of free zinc ions, amyloid precursor protein （APP） and ZnT6 in the APP/PS1 transgenic mouse cerebellum, respectively. Immunofluorescence and confocal laser scanning microscopy were used to analyze the relation between ZnT6 and Aβ in senile plaques. Results Zinc ions, APP and ZnT6 were mainly located in the amyloid palques, which were predominately located in the molecular layer. The Purkinje cell layer and granular layer only contained a few plaques. Confocal microscopic results revealed a eoloealization of ZnT6 and AJ3 in the senile plaques. Conclusions The abundant expression of ZnT6 and accumulation of zinc ions in theβ- amyloid plaques of the APP/PS1 transgenic mouse cerebellum, suggesting that zinc ions might be involved in the formation of senile plaques, while ZnT6 might play an important role in the regulation of zinc accumulation during the pathological process of Alzheimer＇s disease.

关 键 词：锌离子 锌转运体6(ZnT6) β淀粉样蛋白(Aβ) β淀粉样蛋白前体蛋白(APP) APP/PS1 转基因小鼠 小脑 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]