The Expression and Role of Beta Amyloid Precursor Protein and Beta Amyloid Peptide in Ischemic Brain

在阿尔茨海默病患者的大脑中，β淀粉样蛋白（βAP）是老年斑的主要成分。在缺血应激中，β淀粉样蛋白前体蛋白（APP）和βAP被报道上调。用免疫组织化学方法检测雄性Wister-ST大鼠大脑中动脉闭塞（MCAO） 15、30、2 h后短暂性缺血后APP和βAP的表达和分布。星形胶质细胞和小胶质细胞采用免疫组织化学GFAP、OX42测定。app阳性星形胶质细胞分布于梗死内及周围纹状体、皮层和胼胝体。APP于MCAO后3 ~ 7 d表达。次年，于MCAO 2 h后3、7、14、30、60天再灌注后，取脑组织，进行APP、βAP、Conco红免疫染色。闭塞后3天至60天，观察梗死周围具有APP的反应性星形胶质细胞。在闭塞后7、14和30天，βAP的免疫反应性也局限于梗死外周区的反应性星形胶质细胞。然而，在MCAO后3天或60天未发现β -淀粉样蛋白表达。短暂性缺血暂时诱导反应性星形胶质细胞中β -淀粉样肽的表达，但这种表达在第30天达到峰值，在第60天消失。这些结果表明，β -淀粉样肽来源于同一反应性星形胶质细胞对APP的加工，并在缺血应激后60天内停止生产。

In the brains of Alsheimer' s disease patients, beta amyloid protein (βAP) is the major component of senile plaque. In ischemic stress, beta amyloid precursor protein (APP) and βAP are reported to be upregulated. Using Male Wister-ST rats, expression and distribution Of APP and βAP were examined immunohistochemically after transient ischemia induced by a 15-min, 30-min and 2-h middle cerebral artery occlusion (MCAO). Astrocyte and microglia were determined immunohistochemically by GFAP, OX42. APP-positive astrocytes were distributed at striatum, cortex and corpus callosum in and around the infarction. APP was expressed in 3, 7 days following the MCAO. In the next year, after reperfusion for 3, 7, 14, 30 and 60 days following 2-h MCAO, brains were removed and immunostaining including APP, βAP and Conco red was performed. The reactive astrocytes with APP were observed in the periphery of infarct from 3 days to 60 days post-occlusion. The immunoreactivity of βAP was also localized in the reactive astrocytes in the peripheral zone of infarct at 7, 14, and 30 days post-occlusion. However, beta amyloid expression was not identified at 3 days or 60 days post MCAO. Transient ischemia temporarily induced beta amyloid peptide expression in reactive astrocytes, but this expression peaked at 30 days and disappeared at 60 days. These findings suggested that beta amyloid peptide was derived from the processing of APP produced in the same reactive astrocytes and the production of the peptide stopped within 60 days after the ischemic stress.