| 摘要: |
| 目的:分析糖尿病大鼠认知行为学改变与脑组织β-淀粉样蛋白(β-amyloid protein,Aβ)、环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)及磷酸化CREB(phosphorylated CREB，pCREB)表达变化的相关性，为探讨糖尿病糖代谢异常在阿尔茨海默病发病中的作用机制奠定基础。方法:腹腔注射链脲佐菌素(streptozocin,STZ)诱发糖尿病大鼠动物模型，随机分为4周模型组(M4组)、6周模型组(M6组)、8周模型组(M8组),以同批未制模大鼠作为正常对照(N组)。穿梭箱实验、Morris水迷宫实验检测认知行为学改变，刚果红染色检测大鼠脑内淀粉样物质沉着，Western印迹法、酶联免疫吸附法和RT-PCR检测大鼠脑组织CREB与pCREB的表达，酶联免疫吸附法检测脑组织Aβ表达。结果:行为学检测显示模型组大鼠有显著的认知功能障碍，模型组与正常对照组比较有明显差异(P<0.01)；模型组Aβ表达明显增高(P<0.01)，模型组CREB与pCREB表达明显降低(P<0.01)，而3个模型组比较无统计学差异；Aβ表达水平与CREB、pCREB表达水平负相关，Aβ与学习、记忆损伤正相关，CREB、pCREB与学习、记忆损伤负相关。结论:糖尿病糖代谢异常可能通过下调脑组织CREB、pCREB表达及增强Aβ表达诱发脑损伤，导致认知行为改变。 |
| 关键词: 糖尿病 阿尔茨海默病 β-淀粉样蛋白 环AMP反应性DNA结合蛋白质 |
| DOI：10.3724/SP.J.1008.2009.0684 |
| 投稿时间：2008-09-28修订日期：2009-01-08 |
| 基金项目:国家民政部中国老年学学会资助课题(2007-18-3-05). |
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| Expression of cAMP responsive element binding protein and β-amyloid protein in cerebral tissues of diabetic rats |
| CAI Zhi-you1,YAN Ning1,YAN Yong1*,HUANG Liang-guo2,LI Jie-ying1,WANG Feng-ying2 |
| (1.Department of Neurology,the First Affiliated Hospital of Chongqing Medical University,the Key Laboratory of Neurological Disorders,Chongqing 400016,China;2.Department of Neurology,The Affiliated Hospital of Zunyi Medical College,Zunyi 563003) |
| Abstract: |
| Objective:To analyze the association of recognition and behavior of diabetic rats with the expression of β-amyloid protein (Aβ) and cAMP response element binding protein (CREB),so as to pave a way for studying the role of diabetic metabolic disorder in the mechanism of Alzheimer’s disease.Methods:Animal model of diabetes mellitus was established by intraperitoneal injection of streptozocin.Wistar rats were randomly divided into normal control groups(N),4 week diabetes mellitus model group (M4),6 week diabetes mellitus model group (M6),and 8 week diabetes mellitus model group(M8).The changes of recognition and behavior were tested by Morris water maze task and shuttle box task.Congo red staining was used to detect the deposition of beta-amyloid in the brain tissues.Expression of Aβ was measured by enzyme linked immunosorbent assay.CREB and pCREB were tested by enzyme linked immunosorbent assay,RT-PCR,and Western blotting assay.Results:Behavioral tests showed that the learning ability and memory of animals in the diabetes mellitus model groups were impaired and significantly decreased compared with those in the normal control group(P<0.01).Compared with the normal control group,the model groups showed higher Aβ expression and lower CREB and pCREB expression (P<0.01),with no significant difference found between the three model groups.The expression of Aβ was negatively correlated with the expression of CREB and pCREB,and was positively correlated with learning and memory impairment of animals.CREB and pCREB were negatively correlated with the learning ability and memory impairment of animals.Conclusion:Diabetes mellitus can contribute to Alzheimer’s disease through increasing expression of Aβ and decreasing expression of CREB and pCREB. |
| Key words: diabetes mellitus Alzheimer’s disease β-amyloid protein cyclic AMP-response DNA-binding protein |
