摘要
目的观察糖尿病大鼠脑组织β-淀粉样蛋白(Aβ)、β-淀粉样前体蛋白(APP)表达,探讨糖尿病糖代谢异常在阿尔茨海默病中的作用机制。方法腹腔注射链脲佐菌素(STZ)诱发糖尿病大鼠动物模型,随机分组:正常组(N组)、假手术组(S组)、4周模型组(M4组)、6周模型组(M6组)、8周模型组(M8组)。穿梭箱实验、Morris水迷宫实验检测认知行为学改变,蛋白质免疫印迹法、RT-PCR和酶联免疫吸附法检测APP,酶联免疫吸附法检测Aβ,用图像分析仪测定光密度值。结果模型组与正常组、假手术组比较有明显差别(P<0.01),模型组APP、Aβ表达明显增高。3个模型组比较无显著性差异,Aβ与APP正相关,APP表达水平与学习、记忆损伤负相关,Aβ与学习、记忆损伤正相关。结论APP、Aβ在糖尿病大鼠脑组织表达增高,糖尿病糖代谢异常增强Aβ表达参与了阿尔茨海默病的发病机制,APP具有双重作用机制,既具有脑保护作用,又有增高Aβ表达作用。
Objective To investigate the expressions of β-amyloid precursor protein （APP） and β-amyloid protein （Aβ） in the brain of diabetic rats, and to explore the mechanism of glucose metabolic disorder in Alzheimer＇s disease. Methods The rat model of diabetes mellitus was established by intraperitoneal injection of streplozocin. The rats were randomly divided into normal group （group N）,sham operation groups （group S）,4-week diabetic model group （group M4）, 6-week diabetic model group （group M6）, and 8-week diabetic model group （group M8）. The changes in behavior were detected with Morris water maze and shuttle box. The expression of Aβ was measured by enzyme-linked immunosorbent assay, and the expression of APP was determined by enzyme-linked immunosorbent assay, Western blot, and RT- PCR. The light density was measured by image analysis. Results The expressions of Aβ and APP in groups M4, M6, and M8 were significantly higher than those＇ in groups N and S （P 〈 0.01 ）. No significant difference was found in the expressions of Aβ and APP between groups M4, M6, and M8. The expression of APP was negatively correlated with cognitive impairment, and the expression of Aβ was positively correlated with cognitive impairment. Conclusion The expressions of Aβ and APP increase in the brain of diabetic rats. The glucose metabolic disorder in diabetes mellitus contributes to Alzheimer＇ s disease by increasing the expression of Aβ but not APP.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2008年第5期644-647,共4页
Journal of China Medical University
关键词
糖尿病
淀粉样前体蛋白
Β-淀粉样蛋白
diabetes mellitus
β-amyloid precursor protein
β-amyloid protein
