糖尿病大鼠认知功能及海马组织GFAP、IL-1β、TNF-α和Aβ表达  

Cognitive function and expression of GFAP,IL-1β,TNF-α and Aβ in hippocampal tissues of diabetic rats

作　　者：蔡志友[1] 晏勇[1] 张骏[2] 黄良国[2] 吴芳[1] 李洁颖[1] 

机构地区：[1]重庆医科大学附属第一医院神经内科重庆市神经病学重点实验室,重庆400016 [2]遵义医学院附属医院神经内科,遵义563003

出　　处：《上海交通大学学报（医学版）》2009年第2期130-134,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家民政部中国老年学学会项目(2007-18-3-05)~~

摘　　要：目的研究糖尿病大鼠认知功能的变化及其海马组织胶质纤维酸性蛋白(GFAP)、IL-1β、TNF-α和β-淀粉样蛋白(Aβ)的表达,探讨糖代谢异常在阿尔茨海默病(AD)发病中的可能作用。方法30只Wistar大鼠随机分为正常组、假手术组和模型组。模型组大鼠腹腔注射链脉佐菌素诱导建立糖尿病大鼠模型,随后根据建模后时间分为模型4、6、8周组。穿梭箱实验、Morris水迷宫实验检测各组大鼠认知行为学改变;ELISA法、Western blotting和免疫组化法检测各组大鼠海马组织GFAP、IL-1β、TNF-α和Aβ表达,并进行相关性分析。结果与正常组和假手术组比较,各模型组大鼠遭受电击次数显著增加,而主动逃避次数显著减少;学习和记忆潜伏期显著增加;组间比较差异有统计学意义(P<0.01)。模型组大鼠海马GFAP、IL-1β、TNF-α、Aβ表达明显增加,与正常组和假手术组比较差异有统计学意义(P<0.01)。上述检测指标在各模型组组间比较,差异无统计学意义(P>0.05)。相关性分析表明,Aβ表达与记忆潜伏期呈显著正相关;GFAP、IL-1β、TNF-α表达与Aβ表达呈显著正相关。结论糖尿病大鼠认知功能受损,其程度与Aβ表达呈正相关;糖尿病大鼠海马组织GFAP、IL-1β、TNF-α表达与Aβ表达均显著增高,且呈正相关。糖代谢异常可能通过激活星形胶质细胞释放炎症因子使Aβ表达增加而参与AD的发病。Objective To explore the changes in cognitive function and detect the expression of glial fibrillary acidic protein （GFAP） , interleukin-1β （IL-1β） , tumor necrosis factor-α （TNF-α） and β-amyloid peptide （Aβ） in hippocampal tissues of diabetic rats, and explore the possible roles of glycometabolism disorder in the pathogenesis of Alzheimer＇s disease （AD）. Methods Thirty Wistar rats were randomly divided into normal group, sham-operation group and model group. Rat models of diabetes mellitus were established by intraperitoneal injection of streptozocin, and were subdivided into model 4 week group, model 6 week group and model 8 week group according to time of model establishment. Changes in cognitive behavior were examined with shuttle box task and Morris water maze test. The expression of GFAP, IL-1β, TNF-α and Aβ was detected by ELISA, Western blotting and immunohistochemistry, and correlation analysis was conducted. Results Compared with normal group and sham-operation group, the times of electric shock, latency of memory and latency of learning were significantly increased, while the times of escape were significantly decreased in each model subgroup （P 〈 0.01 ）. The expression of GFAP, IL-1β, TNF-α and Aβ in hippocampal tissues in model group was significantly higher than that in normal group and sham-operation group （ P 〈 0.01 ）. However, there was no significant difference in the above parameters among model subgroups （P 〉 0.05）. It was revealed by correlation analysis that the expression of Aβ was positively correlated with the latency of memory, and the expression of GFAP, IL-1β and TNF-α was positively correlated with the expression of Aβ. Conclusion There exists impairment of cognitive function in diabetic rats, and the degree of impairment is positively correlated with the expression of Aβ. The expression of GFAP, IL-1β and TNF-α in hippocampal tissues of diabetic rats increases and is positively correlated with the expression of Aβ, which als

关 键 词：糖尿病 星形胶质细胞 炎症 Β-淀粉样蛋白 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R363.2[医药卫生—临床医学]