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
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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.
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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[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.
[2]J. Hort, J. T. O'Brien, G. Gainotti, et al.EFNS guidelines for the diagnosis and management of Alzheimer's disease. European Journal of Neurology,2010,3:1468-1331.
[3]田金洲.阿尔茨海默病的病理生理；田金洲.阿尔茨海默病的诊断与治疗.人民卫生出版社,2009,12：65-80.
[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.
[6]王永炎.中医对老年期痴呆发病机理的思考；陈可翼.老年性痴呆发病机理与诊治.北京医科大学中国协和医科大学联合出版社,1998,12：80-99.
[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.
[8]Holger WiUe,Gerard Drewes,Jacek Biernat.Alzheimer-like Paired Helical Filaments and Antiparallel Dimers.Formed from Microtubule-associated Protein Tau In Vitro.The Journal of Cell Bio logy, Volume 118,Number 3, August 1992 573-584.
[9-]Grundke-Iqbal I, Iqbal K, Tung et al. Abnormal phosporylation of microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Prpc Natl Acad Sci USA,1986,83:4913-4917.
[10]王建枝,王丹玲.tau蛋白形成NFT的机制；盛树力.老年性痴呆及相关疾病.科学技术文献出版社,2006,4：267-282.
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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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[3]田金洲.阿尔茨海默病的病理生理；田金洲.阿尔茨海默病的诊断与治疗.人民卫生出版社,2009,12：65-80.
[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.
[6]王永炎.中医对老年期痴呆发病机理的思考；陈可翼.老年性痴呆发病机理与诊治.北京医科大学中国协和医科大学联合出版社,1998,12：80-99.
[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.
[8]Holger WiUe,Gerard Drewes,Jacek Biernat.Alzheimer-like Paired Helical Filaments and Antiparallel Dimers.Formed from Microtubule-associated Protein Tau In Vitro.The Journal of Cell Bio logy, Volume 118,Number 3, August 1992 573-584.
[9-]Grundke-Iqbal I, Iqbal K, Tung et al. Abnormal phosporylation of microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Prpc Natl Acad Sci USA,1986,83:4913-4917.
[10]王建枝,王丹玲.tau蛋白形成NFT的机制；盛树力.老年性痴呆及相关疾病.科学技术文献出版社,2006,4：267-282.
[11]Gail V.W. Johnson and William H.Stoothoff. Tau phosphorylation in neuronal cell function and dysfunction. Journal of Cell Science 117,5721-5729.doi:10.1242/jcs.01558.
[12]Khatoon S, Grundke-Iqbal I,Iqbal K.Brain levels of microtubule-associated protein tau are elevated in Alzheimer disease: a radioimmuno-slot-blot assay for nanograms of the protein,J Neurochem, 1992,59:750-753.
[13]Arriagada P V, Growdon J H, Hedley-Whyte E T,et al. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease[J]. Neurology,1992,42:631-639.
[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.
[15]Iqbal K, Grundke-Iqbal I,Alzheimer neurfibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med,2008,12 (1):38-55.
[16]刘世杰,王建枝.tau蛋白的结构、功能和异常修饰与阿尔茨海默病的关系；盛树立.老年痴呆发病机理与药理研究.科学技术文献出版社,2003,10：107-121.
[17]裴进京.阿尔茨海默病神经纤维退行性变及缠结的形成机制；盛树立.老年性痴呆：从分子生物学到临床诊治.科学技术文献出版社,1998,10：205-215.
[18]王建枝, Grundke-Iqbal I,Iqbal K.Alzheimer病神经原纤维退化的T异常学说；陈可翼.老年性痴呆发病机理与诊治.北京医科大学中国协和医科大学联合出版社,1998,12：80-99.
[19]陈生弟,马国诏.阿尔茨海默病的信号转导机制；盛树力.老年性痴呆及相关疾病.科学技术文献出版社,2006,4.
[20]庄蕾,于布为.Cdk5与学习和记忆的研究进展.生理科学进展2010年第41卷第2期141-143.
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