二苯乙烯苷对D-半乳糖致拟痴呆小鼠学习记忆和海马APP、Aβ表达的影响

目的观察二苯乙烯苷(TSG)对D-半乳糖致拟痴呆小鼠学习记忆能力及海马β淀粉样蛋白前体(APP)、β淀粉样蛋白(Aβ)表达的影响。方法连续给昆明种小鼠灌胃TSG 50天,同时每天颈部皮下注射D-半乳糖建立痴呆小鼠模型,以Morris水迷宫为学习记忆评价指标,并采用免疫组化及图像分析测定各组小鼠海马组织APP、Aβ平均光密度和阳性细胞数。结果在隐蔽平台试验中拟痴呆小鼠表现出明显的学习记忆障碍,逃避潜伏期显著延长(P<0.05),TSG各剂量组逃避潜伏期较模型组显著缩短(P<0.05);探索试验中TSG各剂量组原平台象限的停留时间和穿越原平台次数明显多于模型组。与模型组比较,TSG各剂量组能降低拟痴呆小鼠脑内APP、Aβ平均光密度值和阳性细胞数(P<0.05)。以上效应均呈现一定的量效关系。结论TSG各剂量能明显地改善拟痴呆小鼠的学习记忆能力,能减少或抑制APP、Aβ的过度产生,保护神经元免受Aβ的神经毒性。

Effects of TSG on learning and memory abilities and expressions of APP and Aβ in hippocampus of mice with dementia induced by D-galactose

Objective To study the effects of 2, 3, 5, 4＇ -tetrahydroxy-stilbene-2-O-β-D-glylcoside （TSG） on learning and memory abilities and expressions of β- amyloid precursor protein （APP） and β- amyloid （Aβ） in hippocampus of mice with dementia induced by D- galactose. Methods After the mice were treated with intragastric administration with TSG for 50 days continually, the mice were treated subcutaneous injection with D- galactose at the same time to establish the dementia model, then the Morris water maze test was performed to survey the learning and memory abilities, and the immunohistochemical analysis and .computerized image presentation analy- sis system were used to determine the APP and Aβ average optical density and their imrnunoreactive neurons in hip-pocampus. Results The mice with dementia had learning and memory disorders during hidden platform test, and the escape latency were significantly longer than that of TSG - treated groups （ P 〈 0.05）. TSG - treated groups could significantly prolong the staying time and the frequency of crossing original platform quadrant in spatial probe test （ P 〈0.05）. Compared with model group, TSG-treated groups could decrease significantly the APP and Aβ average optical density and their immunoreactive neurons in hippocampus of mice with dementia via immunohistochemical analysis （ P 〈 0.05）. All the data showed a dose - response relationship to some degree. Conclusion TSG can improve the learning and memory abilities in mice with dementia and reduce or inhibit the over-expression of APP and Aβ in hippocampus of mice with dementia, so as to protect the neurons from the neurotoxicity of Aβ.