Ⅰ型糖尿病脑病模型大鼠空间学习记忆以及海马齿状回细胞凋亡和Bax与Bcl-2蛋白表达的变化  

Changes in spatial learning and memory as well as in cell apoptosis and Bax and Bcl-2 protein expressions in the hippocampal gyrus of rat with type 1 diabetic encephalopathy induced by streptozotocin

作　　者：玉洪荣[1] 王薇[1] 郭灵[1] 张芳[1] 蓝玲[1] 白鹭[1] 

机构地区：[1]广西医科大学人体解剖学教研室,广西南宁530021

出　　处：《解剖学研究》2009年第3期161-164,F0004,共5页Anatomy Research

基　　金：广西科学基金资助项目(桂科自0542069)

摘　　要：目的探讨1型糖尿病脑病海马齿状回细胞凋亡、Bax与Bcl-2蛋白表达、空间学习记忆之间的相互关系。方法通过腹腔注射链脲佐菌素(溶于柠檬酸缓冲液)建立1型糖尿病脑病模型大鼠,通过腹腔注射柠檬酸缓冲液建立载体模型大鼠。应用Morris水迷宫、TUNEL技术、Bax与Bcl-2免疫组化方法,观察各组大鼠海马齿状回颗粒下区(SGZ)、颗粒细胞层(GCL)的Bax、Bcl-2、TUNEL阳性细胞和空间学习记忆的变化。结果糖尿病脑病组大鼠的SGZ、GCL的Bax阳性细胞数、TUNEL阳性细胞数、水迷宫的逃避潜伏期和游泳距离均明显高于载体模型组或正常对照组大鼠的对应指标(P<0.01);而糖尿病脑病组大鼠的Bcl-2阳性细胞数则明显低于载体模型组或正常对照组大鼠(P<0.01),但以上各组3类阳性细胞的形态和分布却均无明显差异。结论体内长期缺乏胰岛素可打破凋亡基因Bax与抗凋亡基因Bcl-2的蛋白表达水平之间原有的正常动态平衡状态,致使海马齿状回的细胞倾向于多发生细胞凋亡事件,这可能是引发1型糖尿病脑病神经发生障碍及空间学习记忆异常的一个因素。Objective To investigate the interrelationships among cell apoptosis, Bax or Bcl-2 protein expression in hippocampal dentate gyrus as well as learning and memory of type 1 diabetic encephalopathy rat. Methods The rat model of type 1 diabetic eneephalopathy was established by intraperitoneal injection of streptozotoein （dissolved in vehicle solution）. The rat vehicle control model was established by intraperitoneal injection of vehicle solution. After the above rat models were established, Morris water maze, Bax or Bcl-2 immunohistochemistry, terminal-deoxynucloetidyl-transferase-mediated-dUTP nick and labeling （TUNEL） technique were separately used to detect the abilities of learning and memory, the cell apoptosis, and the Bax or Bcl-2 protein expression in hippocampal dentate gyrus of each rat group. Results The numbers of TUNEL positive cells and Bax positive cells in the subgranular zone （SGZ） or granular cell layer （GCL） in the hippocampal dentate gyrus of type 1 diabetic encephalopathy model rats were significantly higher than those in vehicle control model rats or intact control rats. However, The abilities of spatial learning and memory as well as the number of Bcl-2 positive cells in SGZ or GCL of type 1 diabetic encephalopathy model rats were significantly decreased in comparison of those in vehicle model rats or in intact control rats （P〈0.01）. Conclusion The abnormal imbalances in expressions of anti-apoptotic gene Bcl-2 and apoptotic gene Bax induced by a long-termed lack of insulin enhance cell apoptosis in the hippoeampal dentate gyrus, which may be one factor for causing neurogenesis disorders in SGZ or GCL and for impairments in spatial learning and memory of rats with type 1 diabetic encephalopathy.

关 键 词：糖尿病脑病 学习记忆 细胞凋亡 BAX Bcl-2 神经发生 齿状回 海马 大鼠 

分 类 号：R587.1[医药卫生—内分泌] R747.9[医药卫生—内科学]