摘 要:阿尔兹海默病（Alzheimer’s disease，AD ）是一种以智力缓慢丧失为特征的神经退行性疾病。尽管人们已经知道Aβ的聚集能导致引起tau蛋白的过度磷酸化，但其中的详细机制尚有待深入研究，根据前人实验结果得知，Aβ导致tau蛋白磷酸化的过程中，还有一种蛋白参与了此调节过程，即GSK-3β蛋白，此蛋白的活性直接影响tau蛋白的磷酸化，随着人们对治疗药物的深入了解，发现壳寡糖是一种良好的Aβ聚集抑制剂。

　　　目的：研究壳寡糖对由Aβ诱导的tau磷酸化细胞信号通路的影响。

　　　方法：通过显微镜观察细胞形态的变化，MTT法测细胞存活率以及Western检测tau/p-tau,PI3K/p-PI3K蛋白含量变化等方法，研究壳寡糖对由Aβ诱导的tau磷酸化细胞信号通路的影响。

　　　结果：损伤组随Aβ浓度增加细胞逐渐突触减少呈圆形，cos保护组较损伤组完好。MTT实验结果显示Aβ1-40(5μM)作用24h后能明显降低SY5Y细胞存活率(44.3%,P<0.01),壳寡糖(100, 200, 400μg/ml )对损伤的SY5Y细胞存活率下降有一定的抑制作用。Western blot分析显示，壳寡糖短时间(3h内)单独作用SY5Y细胞会使tau和PI3K蛋白磷酸化水平降低, Aβ1-40作用(20h) SY5Y细胞会使tau和PI3K蛋白磷酸化水平持续升高。壳寡糖和Aβ1-40共同作用(20h) SY5Y细胞发现tau和PI3K蛋白磷酸化水平下降。 

　　　结论：壳寡糖有助于缓解Aβ25-35引起的神经毒性。COS可以减轻AB1-40所诱导的SY5Y细胞tau和PI3K蛋白磷酸化.

关键词：壳寡糖，阿尔茨海默病，β-淀粉样蛋白，人神经母细胞瘤细胞，tau蛋白，过度磷酸化,磷脂酰肌醇3激酶 

Abstract:Alzheimer's disease (AD) is a characteristics of slow loss of intellectual neurodegenerative diseases. Although people already know that the aggregation of Aβ can lead to cause hyper-phosphorylation of tau protein, but the detailed mechanism remains to be in-depth study of Aβ cause. According to previous experimental results, the process of tau phosphorylation is adjustment process which is GSK-3β protein involved in.GSK-3βprotein's activity directly affect the phosphorylation of tau protein, with the in-depth understanding of the therapy, found that Chitosan Oligosaccharide is a good inhibitor of Aβ aggregation 

　　　OBJECTIVE : The purpose of this experiment is to observe the effect of chitosan oligosaccharide on SH-SY5Y cell tau protein hyperphosphorylation induced by Aβ.

　　　METHODS: Through the observation of cell morphology, cell survival rate determination, through Western blot to detect the expression of tau/p-tau and PI3K/p-PI3K Results, research on the effect of chitosan oligosaccharide on SH-SY5Y cell tau protein hyperphosphorylation induced by Aβ

　　　RESULT：with hydrogen peroxide concentration increases ，Injuries group cell cynapse reduces  gradually, protection group cell well. MTT assay results showed that Aβ1-40(5μM) could significantly reduce SY5Y cells activity (44.3%, P<0.01). Chitooligosaccharides (100, 200, 400μg/ml) could increase SY5Y cell viability induced by Aβ1-40 . Western blot analysis showed that SY5Y cells treated with chitooligosaccharides alone (3h), phosphorylated tau and PI3K levels reduce , treated with Aβ1-40 for 20 hours phosphorylated tau and PI3K levels continued to rise. Chitooligosaccharides and Aβ1-40 together treated with SY5Y cells tau and PI3K protein phosphorylation levels reduce . 

　　　CONCLUSION: chitooligosaccharides contribute to alleviate the Aβ1-40 induced neurotoxicity . COS could attenuate AB1-40-induced tau and pi3k protein phosphorylation .

Key word：chitosan oligosaccharide，AD，Aβ(β-amyloid)，SH-SY5Y，tau protein，Hyperphosphorylation，PI3K