【作者】 姜波；

【导师】 苏云明；

【作者基本信息】 黑龙江中医药大学 ， 中西医结合基础， 2010， 博士

【摘要】 目的:本课题围绕NF-κB/IκB-α通路及星形胶质细胞理论观察补阳还五汤胶囊对老年性痴呆(AD)模型大鼠神经细胞的保护作用,并进一步探讨其作用机制。方法:本课题采用大鼠单侧海马区定向注射Aβ1-40复制AD动物模型,观察补阳还五汤胶囊对AD模型大鼠的行为学的影响,通过HE染色及透射电镜观察病理形态学变化,并以酶联免疫法检测血清中Aβ1-40和β-APP含量的变化,通过免疫组化法检测对AD大鼠脑组织海马区NF-κBp65、IκB-α、GFAP和S100β蛋白表达的影响,此外还通过实时荧光定量PCR技术观察NF-κBp65mRNA、IκB-αmRNA和BACE1mRNA基因表达的影响,从行为学、细胞及分子水平探讨补阳还五汤胶囊对阿尔茨海默病的神经细胞保护作用。结果:1.大鼠行为学实验显示补阳还五汤胶囊可以明显改善模型动物行为学的异常,提高学习记忆能力。2.补阳还五汤胶囊能改善病理因素造成的实验动物脑内的组织形态的异常。3.补阳还五汤胶囊能明显降低AD大鼠血清中Aβ1-40和β-APP含量。4.补阳还五汤胶囊能抑制AD大鼠大脑海马区中GFAP、S100β及NF-κBp65蛋白的表达,促进IκB-α蛋白的表达。5.补阳还五汤胶囊能促进AD大鼠大脑海马区IκB-αmRNA基因的表达,降低NF-κBp65mRNA及BACE1mRNA基因的表达。结论:补阳还五汤胶囊对AD大鼠的神经元具有保护作用,其机理可能是通过降低AD大鼠的核转录因子NF-κBp65,从而抑制星形胶质细胞的增生并降低胶质细胞相关蛋白GFAP、S100β的表达,同时抑制BACE1的转录和翻译,降低对APP的活性,最终减少Aβ1-40的生成,从而达到预防并治疗痴呆的目的。更多还原

【Abstract】 Objective: The issue surrounding the NF-κB / IκB-αpathway and the theory of astrocytes observed Buyang Huanwu Decoction capsule on Alzheimer’s disease (AD) rat model nerve cell injury and further explore its mechanism.Methods: Targeted by rats with bilateral hippocampal injection of Aβ1-40 to copy AD rat model , observed Buyang Huanwu Decoction capsule on behavior infection of AD rat model, observed morphological changes by HE staining and transmission electron microscopy , determined serum Aβ1-40 andβ-APP content changes by ELISA, determined NF-κBp65, IκB-α, GFAP and S100βprotein expression by immunohistochemistry, observed NF-κBp65mRNA, IκB-αmRNA and BACE1mRNA gene expression by Real time PCR , discussed Buyang Huanwu Decoction capsule protect effect nerve cells of AD from the Behavior, cellular and molecular level.Result: 1. Rat behavior experiment Buyang Huanwu Decoction capsule can significantly improve the abnormal animal behavior models, improve learning and memory. 2. Buyang Huanwu Decoction capsule can improve the brain of experimental animals by pathological factors, the abnormal morphology. 3. Buyang Huanwu Decoction capsules can significantly reduce AD rat serum Aβ1-40 andβ-APP levels. 4. Buyang Huanwu Decoction capsule can inhibit the AD hippocampus of rat brain GFAP, S100βand NF-κBp65 protein expression, the promotion of IκB-αprotein. 5. Buyang Huanwu Decoction capsule can promote AD rat hippocampus IκB-αmRNA gene expression, decreased NF-κBp65mRNA and BACE1mRNA genes.Conclusion: Buyang Huanwu Decoction capsule has a protective effect on rat neurons in AD, the mechanism may be the AD rats by reducing nuclear transcription factor NF-κBp65, thereby inhibiting the proliferation of astrocytes and reduced glial cell associated protein GFAP, S100βexpression, and inhibition of BACE1 transcription and translation of the APP activity and ultimately reduce the formation of Aβ1-40, thus preventing the occurrence and treatment of dementia.更多还原