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脑中，β淀粉样蛋白（βAP）是老年斑的主要成分。据报道，在缺血应激中，β淀粉样前体蛋白（APP）和βAP上调。采用雄性Wister-ST大鼠，以大脑中动脉阻塞（MCAO）15 min、30 min和2 h造成短暂性脑缺血，用免疫组织化学方法检测脑内APP和βAP的表达和分布。星形胶质细胞和小胶质细胞采用GFAP、OX 42免疫组化染色。APP阳性星形胶质细胞分布于梗死灶内及周围的纹状体、皮质和胼胝体。APP在MCAO后3、7天表达。第二年，分别于MCAO 2 h后再灌注3、7、14、30和60 d，取脑行APP、βAP和Conco red免疫组化染色。缺血后3 ~ 60天，梗死灶周围可见APP反应性星形胶质细胞。在缺血后7、14和30天，βAP的免疫反应也定位于梗死周边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。短暂性脑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30天达到峰值，并在60天消失。这些发现表明，β淀粉样肽来源于相同反应性星形胶质细胞中产生的APP的加工，并且该肽的产生在缺血应激后60天内停止。

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.