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β-淀粉样蛋白对D-半乳糖致衰老大鼠学习记忆及海马超微结构的影响

张 葳1, 张 昱1*, 赵 晴2, 杨永梅1   

  1. 1. 吉林大学第一医院神经内科, 吉林 长春130021;2. 吉林大学中日联谊医院神经内科,吉林 长春130031
  • 收稿日期:2004-11-05 修回日期:1900-01-01 出版日期:2005-03-28 发布日期:2005-03-28
  • 通讯作者: 张 昱

Effects of β-amyloid on learning-memory and hippocampus neuron ultrastructures in aging rats induced by D-galactose

ZHANG Wei1,ZHANG Yu1*,ZHAO Qing2,YANG Yong-mei1   

  1. 1. Department of Neurology, First Hospital, Jilin University, Changchun 130021, China;2. Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun 130031, China
  • Received:2004-11-05 Revised:1900-01-01 Online:2005-03-28 Published:2005-03-28
  • Contact: ZHANG Yu

摘要: 目的:观察β-淀粉样蛋白对D-半乳糖(D-gal)致衰老模型大鼠学习记忆能力和海马神经元超微结构的影响。 方法:将水迷宫筛选反应迅速、活跃的48只大鼠随机分为4组(n=12),即生理盐水对照组、Aβ组、D-gal组和联合模型组(Aβ+D-gal组)。生理盐水对照组每天腹腔注射生理盐水1 mL,连续6周,于第7周双侧海马内注射生理盐水1 μL。Aβ组第1~6周腹腔注射同生理盐水组,于第7周双侧海马内注射Aβ 1 μL。D-gal组第1~6周腹腔注射D-gal 50 mg•kg-1•d-1,于第7周双侧海马注射生理盐水1 μL。联合模型组腹腔注射D-gal 50 mg•kg-1•d-1,于第7周双侧海马内注射Aβ25-351 μL。检测造模前后各组水迷宫逃避潜伏期成绩,并用电镜观察海马神经元超微结构的改变。 结果:①造模后1周Aβ组、D-gal组、D-gal+Aβ组逃避潜伏期较造模前均延长,以D-gal+Aβ组变化最明显(P<0.01),而生理盐水对照组变化不明显。经统计学处理显示,造模后Aβ组、D-gal组、D-gal+Aβ组各组大鼠逃避潜伏期跟造模前及生理盐水对照组比较差异均有显著性,Aβ组和D-gal组与造模前及生理盐水对照组比较差异具有显著性(P<0.05),D-gal+Aβ组与造模前及生理盐水对照组比较差异具有显著性(P<0.01)。②生理盐水对照组大鼠海马神经细胞结构基本正常,Aβ损伤组海马神经细胞线粒体嵴断裂,D-gal损伤组细胞质内可见较多脂褐素颗粒沉积,Aβ+D-gal组可见神经细胞核固缩,线粒体肿胀,可见嵴断裂,空泡形成,核染色质浓缩趋边凝聚、致密、深染,甚至出现空化,细胞质内有较多脂褐素颗粒沉积。 结论:D-gal与 Aβ联合使用可导致脑老化程度加重,学习记忆能力显著减弱。

关键词: 学习, 记忆, 半乳糖, 衰老, 阿尔茨海默病

Abstract: Objective To investigate the effects of β-amyloid on learning memory and hippocampus neuron ultrastructures in aging rats induced by D-galactose (D-gal). Methods Using the water labyrinth test, the rats with quickly reaction were selected and randomly divided into four groups(n=12):control group,Aβ group,D-gal group, and D-gal+Aβ group. In the D-gal group and D-gal+Aβ group, each animal was injected intraperitoneally with the D-gal 50 mg•kg-1•d-1 for 6 weeks, the decrepitude animal model was established. In the control group and Aβ group, each animal was injected intraperitoneally with same quantity of physiology saline. At the 7th week, the rats in Aβ group and D-gal+Aβ group were injected with Aβ25-35 into bilateral hippocampal regions, 1 μL in each side; and the rats in control group and D-gal group were injected with same quantity of physiology saline. After the model was established successfully, Morris water maza test was used to determine the ability of learning and memory. Ultrastructures of the hippocampus neurons were observed under electron microscope. Results ①One week after operation, the escape latencies were longer in Aβ group, D-gal group, and Aβ+D-gal group than that in control group (P<0.05),obviously in Aβ+D-gal group (P<0.01). ②The hippocampus neuron ultrastructures in control group were nearly normal, mitochondria cristae of the hippocampus neurons in Aβ group broke. The hippocampus neurons in D-gal group had lipofuscin deposit. In D-gal+Aβ group, nucleuses pyknosis was fonud and chondriosomes swelled. The crista broke and became emptey bubble. Conclusion The combination of D-gal and Aβ can induce a conspicuous reduction of learning-memory ability in rats, and increase the aging degree of brain.

Key words: learning, memory, galactose , aging, Alzheimer disease

中图分类号: 

  • R-332