脑尔康对AD模型小鼠脑内APP,Aβ表达的影响

Protective Effects of Naoerkang on AD Mice Induced by Chronic Al Toxicity Involved in Regulatting Protein Expression of APP and Aβ

目的:观察复方中药脑尔康对慢性铝中毒阿尔茨海默病(AD)模型小鼠学习记忆及脑内淀粉样前体蛋白(APP),β淀粉样蛋白(Aβ)表达的影响,探讨该药抗痴呆的分子机制。方法:60只昆明小鼠随机分为空白对照、模型、西药吡啦西坦、脑尔康高、中、低剂量6组,除空白组外,其余各组均采用氯化铝(AlCl3)溶液以100 mg.kg-1ip造模,空白组给予等量生理盐水ip,3个剂量脑尔康组给予脑尔康(34,17,8.5 g.kg-1.d-1)连续ig 50 d,吡啦西坦组给予吡啦西坦(10 g.L-1)ig,空白组和模型组给予等量生理盐水ig。采用跳台法检测AD模型小鼠学习记忆成绩,用免疫组织化学方法观察脑尔康对AD模型小鼠脑皮层及海马结构区域APP,Aβ表达的影响,对APP,Aβ阳性反应物质采用图像信号采集与分析系统进行灰度分析。结果:与对照组比较,模型组记忆潜伏期明显缩短(P<0.01),学习潜伏期明显延长(P<0.05),学习与记忆的错误次数明显增多(P<0.01);用药各组分别与模型组比较记忆潜伏期明显延长(P<0.01),学习潜伏期明显缩短(P<0.05),学习与记忆的错误次数明显减少(P<0.01)。各用药组模型小鼠脑内APP,Aβ的表达均不同程度减少(P<0.05或P<0.01);脑尔康3个剂量组比较存在明显量效关系。结论:脑尔康对慢性铝中毒AD模型具有显著的抗痴呆作用,其作用机制可能与调控APP,Aβ表达有关。

Objective： To investigate the protective effects of Naoerkang（NEK） on Alzheimer disease（AD） mince induced by chronic Al（AlCl3） toxicity involved in regulating protein expression of amyloid precursor protein（APP） and β-amyloid（Aβ）.Method： Sixty male mice were randomly divided into normal control group,model group,piracetam group,low-dose NEK group,medium-dose NEK group,and high-dose NEK group,with 10 mice in each group,AlCl3（100 mg·kg-1） were injected into abdominal cavity in mice to establish AD model whereas the normal control mice were injected with same volume of saline for comparisom.The mice in the NEK groups were intragastrically treated respectively with high,medium and low dose（1.36,0.68,0.34 g·mL^-1） NEK for 50 days consecutively;piracetam（10 g·mL^-1） was intragastrically administered to mice in the piracetam group;and normal saline was applied in the control and model groups.Jumping stand was used to examine their abilities in learning and memory.The positive protein expression of APP and Aβ in cortex and hippocampal region of the mice in each group were detected by immunohistochemistry,and the results were analyzed by gray scale adopting Qwin550CW images and signals cllection and analysis system.Result： Compared with the control group,the Latent Period of memory was shortened significantly（P〈0.01）,while that of learning had been prolonged obviously（P〈0.05）and the times of mistakes for learning and memory increased significantly（P〈0.01） for the mice of the model group.Compared with the model group,the Latent Period memory in the groups treatment with drug shortened significantly（P〈0.01）,while that of learning had been prolonged obviously（P〈0.05）and the Frequency of Error for learning and memory had been increased evidently（P〈0.01）.The expressions of APP,Aβ in cortex and hippocampus had been increased significantly（P〈0.05 orP〈0.01） for the mice of the model group,and it had shown a more obvious reduction campared with the group using Naoerkang（P〈0.01）.Conclusion： Naoerkang can ameliorate the AD induced by Aβ,the mechanism maybe involve in regulating APP and Aβ.