APP5肽类似物165对老年性痴呆模型大鼠行为学及PSD95和Shank 1表达的影响  

The Effects of Analog 165 of APP 5-mer Peptide on Praxiology,Expression of PSD95 and Shank 1 in Alzheimer Disease Rats

作　　者：陆珊[1] 雷亚平[1] 王蓬文[1] 王蓉[2] 盛树力[2] 田金洲[1] 

机构地区：[1]北京中医药大学东直门医院 [2]教育部神经变性病学重点实验室,北京100053

出　　处：《中国神经免疫学和神经病学杂志》2007年第4期183-186,I0002,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家重点基础研究发展"973"计划基金资助项目(2003CB517104)

摘　　要：目的观察5肽类似物165对老年性痴呆(Alzhei mer disease,AD)模型大鼠学习记忆能力及突触后致密区蛋白95(postsynaptic density95,PSD95)和骨架蛋白Shank1表达的影响。方法将45只大鼠随机分为正常对照组、模型组和5肽类似物165治疗组,模型组和治疗组大鼠按体重3mg/kg行双侧侧脑室链脲佐菌素(streptozotocin,STZ)注射,第3天重复注射建立AD模型,对照组以人工脑脊液代替STZ。术后21d治疗组按体重0.34mg/(kg.d)给予APP5肽类似物165灌胃干预,其余两组以蒸馏水代替。3周后应用Morris水迷宫、免疫组织化学和Western blotting方法检测大鼠的学习记忆能力及PSD95和Shank1的表达。结果5肽类似物165治疗组大鼠的平均游泳时间较模型组明显缩短(P<0.01),且海马PSD95和Shank1阳性神经细胞数及PSD95和Shank1蛋白表达较模型组明显增加(P<0.05)。结论5肽类似物165可显著提高大鼠学习记忆能力,增加大鼠海马PSD95和Shank1表达,表明其对突触功能和可塑性具改善作用。Objective To investigate the effects of Analog 165 of APP 5-mer peptide on praxiology, expression of PSD95 and Shank 1 in Alzheimer disease rats. Methods A total of 45 rats were randomly divided into the normal control group,the model group and the treatment group with analog 165 of APP 5-mer peptide. The rats in the model group and the analog 165 treatment group received intracerebroventricular injection of streptozotocin （STZ） bilaterally with a dose of 3 mg/kg and the injection was repeated on the third day. The rats in the control group injected the artificial cerebrospinal fluid instead of STZ injection. Twenty-one days later, the rats in the analog 165 treatment group administered the analog 165 of APP 5-mer peptide at a dose of 0.34 mg/kg per day with a gastric tube, while those in the other two groups were treated with the same volume of water. After 21 days, rats were tested with Morris water maze for learning and memory abilities, and the expression of PSD95 and Shank 1 in the hippocampus were revealed with immunohistochemistry and Western blotting. Results The swimming time were significantly shorter in the Analog 165 group than in the model group（P〈0.01）. The expression of PSD95 and Shank 1 positive cell numbers and the content of PSD95 and Shank 1 in the hippocampus were both higher in the Analog 165 group than in the model group（P〈0.05）. Conclusions Analog 165 can obviously improve the learning and memory abilities, also increase the expression of PSD95 and Shank 1. Analog 165 may play a role in ameliorating the function and plasticity of synapses.

关 键 词：APP5肽类似物165 链脲佐菌素 PSD95 SHANK 1 老年性痴呆 

分 类 号：R749.1[医药卫生—神经病学与精神病学]