石菖蒲活性成分对双转基因小鼠APP及神经突触超微结构的影响  

Effects of Active Components of Rhizoma Acori Tatarinowii on APP and Synaptic Ultrastructure in Tg-APPswe/ PS1dE9 Mice

作　　者：张春霞[1] 郭俊和[1] 陈云波[1] 闫蓉[1] 王奇[1] 于旭华[1] 魏刚[2] 刘四军[3] 程淑意[1] 

机构地区：[1]广州中医药大学临床药理研究所DME中心,广东广州510405 [2]广州中医药大学新药开发研究中心,广东广州510006 [3]广州中医药大学护理学院,广东广州510006

出　　处：《中药新药与临床药理》2014年第1期18-23,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金："十一五"重大新药创制专项课题(2009ZX09103-429);高等学校博士学科点专项科研基金(20114425110007);广东省高等学校科技创新项目(2012KJCX0032);广东省重大科技专项(2012A080202017);广东省科技计划项目(2010A030100009)

摘　　要：目的探讨石菖蒲活性部位β-细辛醚和丁香酚对APPswe/PS1dE9双转基因小鼠脑内β淀粉样前体蛋白(Amyloid Precursor Protein,APP)表达及神经突触超微结构的影响。方法 3月龄SPF级雄性APPswe/PS1dE9双转基因小鼠12只,随机分为4组:模型组、安理申(以安理申为阳性对照药)组、β-细辛醚组及丁香酚组,每组3只,用同龄同背景APPswe/PS1dE9转基因阴性小鼠3只作为正常对照组。用药4个月后,免疫组织化学染色方法检测大脑内海马及皮层APP表达水平,并采用透射电子显微镜观察海马CA1区神经元及神经突触的超微结构的变化。结果模型组在海马CA1区和皮质的APP阳性面积百分比较正常对照组显著增加(P<0.01)。与模型组比较,安理申组和β-细辛醚组在海马CA1区和皮质的APP阳性面积百分比显著减少(P<0.01);丁香酚组皮质的APP阳性面积百分比显著减少(P<0.01)。透射电子显微镜观察,与正常对照组比较,模型组小鼠海马CA1区神经元神经毡内突触结构表现为大片的轴浆空泡化,突触数量减少,突触界面变短或融合消失,突触小泡数量明显减少,突触前膜、后膜及突触间隙大多模糊不清,突触后成分致密区厚度变薄,典型的突触结构已遭破坏,部分线粒体有轻微破损。安理申组、β-细辛醚组及丁香酚组小鼠海马CA1区神经突触结构与正常对照组比较无明显差异,与模型组比较在细胞器结构、轴浆空泡化、突触数量、突触界面、突触小泡数量及突触结构上均有不同程度的改善。结论β-细辛醚及丁香酚可以抑制APP的过量表达,对与学习记忆密切相关的突触有一定的保护和修复作用。Objective To investigate the effect of active components of Rhizoma Acori Tatarinowii on the APP expression and synaptic uhrastructure in Tg-APPswe/PSldE9 mice. Methods The 3-month-old male Tg-APPswe/ PSldE9 mice were randomly divided into 4 groups, namely model group, β-asarone treated group, eugenol treated group and donepezi treated group, 3 mice per group. In addition, 3 male Tg-APPswe/PSldE9 negatively transgenic mice with the same age and background served as the negative control group（normal group）. After treatment for 4 months, APP expression level in the hippocampal CA1 area and cortex were measured by using immunohistochemistry. The synaptic ultrastructure of hippocampal neuron in mice was observed under electron microscopy. Results Compared with the negatively transgenic mice, the expression of APP in the model group were significantly increased in the hippocampal CA1 area and cortex of the brain（P 〈 0.01）. Compared with the model group, the expression of APP in the hippocampal CA1 area and cortex of donepezil treated group and β-asarone 1Lreated group were both significantly decreased（P 〈 0.01）, and the decrease in the cortex of eugenol treated group was more obvious（P 〈 0.01 ）. Compared with the normal group, the structure and function of neurons organelles and synaptic showed significant damage and dysfunction in the hippocampal CA1 area of model group, showing as massive vacuolization of hyaloplasm, decrease of synapse count, unclear presynaptic membrane, postsynaptie membrane and synaptic cleft, thickening of postsynaptic dense area, destroy of the typical synaptic structure, and slight damage of partial mitochondria. The β-asarone treated group, eugenol treated group and donepezi treated group all showed improvement of neurons organelles and synaptic structure to various degrees in comparison with the model group, and had no obvious difference from the normal group. Conclusion The and significant damage of synaptic in the hippocampus CA1 area of the brain at 7 months of a

关 键 词：阿尔茨海默病 石菖蒲 Β-细辛醚 丁香酚 双转基因小鼠 Β淀粉样前体蛋白 神经突触超微结构 

分 类 号：R285.5[医药卫生—中药学]