胰岛素样生长因子与β-淀粉样蛋白在糖尿病大鼠脑组织中的表达及意义

Expression and significance of insulin-like growth factor 1 and β-amyloid protein in brain of diabetic rat

目的观察糖尿病大鼠脑组织胰岛素样生长因子(IGF-1)、β-淀粉样蛋白(Aβ)表达,探讨糖尿病糖代谢异常在阿尔茨海默病(AD)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、假手术组、4w模型组(M4组)、6w模型组(M6组)、8w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,免疫组化法和ELISA法检测IGF-1、ELISA法检测Aβ在糖尿病大鼠脑组织中的表达,用图像分析仪测定光密度值。结果模型组与正常组、假手术组比较有显著差异(P<0.01),模型组IGF-1、Aβ表达明显增高。三个模型组比较无显著性差异,IGF-1和Aβ表达时间上无相关性,IGF-1蛋白表达水平与学习、记忆呈正相关,Aβ蛋白表达水平与学习、记忆呈负相关。结论IGF-1、Aβ在糖尿病大鼠脑组织表达增高,糖尿病糖代谢异常可以通过胰岛素信号转导系统增强Aβ表达参与AD的发病机制。

Objective To investigate expressions of insulin-like growth factor 1 （ IGF-1 ） and β-amyloid （Aβ） protein in brain of diabetes mellitus （DM） rat, and explore the effect of glucose metabolic disorder on mechanism of Alzheimer＇s disease （AD）. Methods DM models were induced by intraperitoneal injection of streptozocin （STZ）, and the models were divided into normal group （N）, sham-operation group （S）, 4 （M4）, 6 （M6） and 8 weeks model group （MS）. Behavioral changes of rats were tested with Morris water maze and shuttle box task. Expression of Aβ was measured by ELISA and IGF-1 by ELISA and immunohistochemistry in brain tissue. The light density value was measured by imaging analysis. Results The expressions of IGF-1 and Aβ in model groups were higher than those of N and S group （ P 〈 0. 01 ）. The expressions of IGF-1 and Aβ had no obvious difference among model groups （ P 〉 0. 05 ）. The expression of IGF-1 and Aβ had no correlation with time. The level Of Aβ protein had negative correlation with learning and memory, while the level of IGF-1 had positive correlation. Conclusions The expressions of IGF-1 and Aβ in DM rat brain increase. DM glucose metabolic disorder can increase the expression of Aβ by disturbing insulin signal pathway, which contributes to AD.