淫羊藿黄酮对转基因痴呆小鼠脑内突触相关蛋白的影响  

Effects of epimedium flavanoids on synapse related protein in brains of dementia transgenic mice

作　　者：楚晋[1] 张兰[1] 叶翠飞[1] 赵玲[1] 亚白柳[1] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室,教育部神经变性病学重点实验室,北京100053

出　　处：《中华医学杂志》2008年第1期31-35,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目（30472184）;国家重点基础研究发展计划“973”基金资助项目（G2003CB517104）;北京市科技新星计划基金资助项目（H020821390190）;首都医学发展基金资助项目（20023002）;首都医学发展基金资助项目（首发03Ⅲ2Ⅰ）

摘　　要：目的观察10月龄APP转基因模型小鼠脑内突触相关蛋白——突触素（SYP）及突触后致密物质-95（PSD-95）蛋白表达的改变，以及中药有效部位淫羊藿黄酮对转基因小鼠脑内SYP和PSD-95表达的影响。方法用药组小鼠自4月龄开始灌胃给予淫羊藿黄酮小剂量（0．03g·kg^-1·d^-1）、大剂量（0．1g·kg^-1·d^-1）6个月至10月龄，正常对照组、转基因阴性对照组及模型组以同样方式灌胃给予蒸馏水。应用免疫组化及Western印迹方法分别检测海马CA1区、CA3区、齿状回及皮质中SYP的表达以及海马CA1区及皮质中PSD-95的表达。结果与转基因阴性对照组相比，10月龄APP转基因模型小鼠皮质SYP蛋白表达明显较低（降低率为51．3％，P〈0．01）；海马CA1区、CA3区及齿状回SYP阳性细胞的IOD值明显较低（降低率分别为59．1％、57．7％及56．5％，均P〈0．01）。皮质PSD-95蛋白表达明显降低（降低率为36．4％，P〈0．01）；海马CA1区PSD-95阳性细胞数少于对照组（减少率为18．5％，P〈0．05）。灌胃给药6个月后，淫羊藿黄酮小、大剂量组小鼠皮质SYP蛋白表达明显高于模型组（增加率分别为40．0％，P〈0．05和106．4％，P〈0．01）；海马CA1、CA3区及齿状回SYP阳性细胞IOD值均明显增加（均P〈0．01）。淫羊藿黄酮小、大剂量组小鼠皮质PSD-95蛋白表达明显增加（增加率分别为57．3％，P〈0．05和84．3％，P〈0．01）。淫羊藿黄酮大剂量组小鼠海马CA1区PSD-95阳性细胞数明显增加（增加率为22．5％，P〈0．05）。结论淫羊藿黄酮能通过促进突触相关蛋白表达而发挥维护神经元突触正常结构的作用，提示淫羊藿黄酮对改善AD神经元突触损伤状况具有潜在应用价值。Objective To investigate changes of synapse related protein, such as synaptophysin （SYP） and postsynaptic dense material 95 （ PSD-95 ）, in brains of 10 months old transgenic mice, and the effects of Epimedium flavanoids （EF） on expression of SYP and PSD-95 in brain of 10 months old of APP transgenic mice. Methods The mice of drug treated group were administered introgastrically by EF （at low doses of 0. 03 and high dose of 0. 1 g·kg^-1·d^-1） from 4 to 10 months old. The mice of normal group and negative transgene group were administered of distilled water by the same way. The expression of SYP in CA1, CA3, and dentate gyrus （DG） areas of hippocampus and cortex, and PSD-95 in hippocampus and cortex were detected by immunohistochemistry and Western blot respectively. Results Compared to negative transgenic mice, the expression of SYP in cortex was decreased by 51.3% （P 〈0.01 ）. The IOD value of SYP immuno-reactivity cell in CA1, CA3 and DG areas of hippocampus in 10 months old transgenic mice were significantly decreased （the suppression rates were 59. 1% , 57. 7% and 56.5% in CA1, CA3 and DG respectively, all P 〈0. 01 ）. The expression of PSD-95 in cortex decreased by 36.4% （P 〈0. 01 ）. The count of PSD-95 immuno-reactivity cell in CA1 area of hippocampus decreased with the suppression rate of 18. 5% （P 〈0. 05）. After being administered introgastrically by EF for 6 months, the expression of SYP in cortex of EF low doses and high dose group mice increased by 40. 0% （ P 〈 0.05 ） and 106.4% （ P 〈 0. 01 ） respectively in comparison with that of the control group. The IOD value of SYP immuno-reactivity cell in hippocampal CA1, CA3 and DG areas of EF low and high dose group mice were all significantly increased （all P 〈 0. 01 ）. The expression of PSD-95 in cortex of EF low and high dose group mice increased by 57. 3% （ P 〈 0. 05） and 84. 3% （P 〈 0. 01 ） respectively when compare to the control group. The count of PSD-95 immuno-reactivity ceil in

关 键 词：阿尔茨海默病 淫羊藿黄酮 突触素 突触后致密物质 

分 类 号：R686[医药卫生—骨科学]