摘要
目的:
观察金思维提取物对APPV717I转基因小鼠脑内总tau蛋白及cdk5表达水平的影响,以探讨金思维提取物防治阿尔茨海默病的作用靶点。
方法:
将3月龄的APPV717I转基因小鼠随机等分为5组:模型组、盐酸多奈哌齐组和金思维小、中、大剂量组。将同月龄、同遗传背景的C57BL/6J小鼠作为对照组。采取灌胃给药,每日1次,连续治疗8个月。运用免疫组织化学和蛋白质印迹技术检测各组小鼠海马组织内总tau蛋白和cdk5的表达水平,并运用单因素方差分析进行组间差异比较
结果:
1与对照组相比,模型组小鼠海马组织内总tau蛋白和cdk5的表达水平均明显升高(P<0.01);
2与模型组相比,各治疗组小鼠海马组织内总tau蛋白和cdk5表达水平均明显减低(P<0.01,P<0.05);
3各治疗组之间相比,小鼠海马组织内总tau蛋白和cdk5表达水平没有显著性差异(P>0.05)。
结论:
金思维提取物能够减低APPV717I转基因小鼠脑内总tau蛋白和cdk5的表达水平,以此为靶点对阿尔茨海默病具有潜在的治疗效果,但治疗效果不存在剂量依赖性。
Objective:
To establish the expression of total tau protein and cdk5 in hippocampal neurons of APPV717I transgenic mice which are treated with GEPT small, middle and large dosage.In order to discuss the target of GEPT in AD treatment.
Methods:
APPV717I transgenic mice of three months were randomly divided into five groups:model group, Donepezil group and GEPT small, middle and large dosage treated groups. Genetic background and age-matched C57BL/6J mice were used as control group. Each group were intragastric administration once daily for eight months.Immunohistochemistry (IHC) and Western bolting were used to determine the expression level of total tau protein and cdk5 in hippocampal neurons of all the mice.One-way ANOVA were used to compare the differences between groups.
Results:
1 Compared with the control group, the expression level of total tau protein and cdk5 in the model group were significantly increased (P< 0.01);
2 Compared with the model group, in GEPT groups and Donepezil group, the expression levels of total tau protein and cdk5 were obviously decreased(P< 0.01, P< 0.05);
3 In GEPT groups and Donepezil group, the expression levels of total tau protein and cdk5 were similer,with no significant differences(P> 0.05)
Conclus ion:
GEPT can decrease the expression levels of total tau protein and cdk5 in hippocampal neurons of APPV717I transgenic mice.This maybe the potential target of GEPT in AD treatment.But there was no dose-dependent treatment effect.
引文
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[1]田金洲.人类共同面临的挑战;田金洲.阿尔茨海默病的诊断与治疗.人民卫生出版社,2009,12:1-24.
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[4]田金洲,时晶.阿尔茨海默病:一个全新的临床病理单元.中国老年学杂志,2008,28(19):34-37.
[5]田金洲.治疗与管理;田金洲.阿尔茨海默病的诊断与治疗.人民卫生出版社,2009,12:160-233.
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[7]尹龙.金思维提取物对APPV717I转基因小鼠学习记忆能力和突触超微结构的影响.北京中医药大学博士研究生学位论文.2010.
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[14]Iqbal K,Alonso Adel C, Chen S,et al.Tau pathology in Alzheimer disease and other tauopathies[J]. Biochim Biophys Acta,2005,1739(23): 198-210.
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