三种中药有效成分复方对阿尔茨海默病转基因小鼠大脑皮质病理学及超微结构的影响

Effects of a compound of three effective ingredients in Chinese medicinal herbs on cortical pathology and ultrastructure in a transgenic mouse model of Alzheimer's disease

目的:观察淫羊藿、黄芪、葛根有效成分复方对阿尔茨海默病APP/PS1双转基因模型小鼠大脑皮质病理学及超微结构的影响。方法:9月龄雄性APP/PS1双转基小鼠36只,随机等分为模型组、淫羊藿组、黄芪组、葛根组、复方组和deferoxamine组(DFO组,为阳性对照组),9月龄雄性C57小鼠6只作为阴性对照组。淫羊藿组、黄芪组、葛根组、复方组灌胃分别给予120 mg/kg淫羊藿苷、80 mg/kg黄芪甲苷、80 mg/kg葛根素、120 mg/kg淫羊藿苷+80mg/kg黄芪甲苷+80 mg/kg葛根有效成分复方,DFO组肌肉注射给予30 mg/kg DFO,模型组和阴性对照组给予1 ml生理盐水,连续用药30 d。用药结束后,采用尼氏染色、Bielschowsky银染及透射电镜技术观察各组小鼠大脑皮质的病理学变化。结果:尼氏染色显示,淫羊藿组、黄芪组、葛根组小鼠较模型组神经元水肿有所减轻,细胞数量略有增加;复方组和DFO组小鼠皮质神经细胞排列整齐且密集,胞浆中尼氏体丰富,水肿明显改善,细胞数量明显增加。改良Bielschowsky银染显示,模型组小鼠皮质可见大量的老年斑,淫羊藿组、黄芪组和葛根组仍可见一定数量的老年斑,复方组小鼠及DFO组小鼠皮质与模型组、单方组相比老年斑数量减少。透射电镜显示,复方组和DFO组小鼠皮质神经元形态比模型组、淫羊藿组、黄芪组和葛根组整齐,胞浆内可见少量脂褐素。结论:淫羊藿、黄芪、葛根有效成分复方能减少APP/PS1转基因模型小鼠大脑皮质老年斑的沉积,降低神经元的损伤。

Objective： To investigate the effects of a compound of epimedium,astragalus and radix puerariae on the cortical pathological and ultrastructural changes in the APP / PS1 double transgenic mouse model of Alzheimer＇s disease（ AD）.Methods： A total of thirty-six specific-pathogen-free male APP / PS1 double transgenic mice aged 9 months were equally and randomly assigned to model,epimedium,astragalus,radix puerariae,compound and deferoxamine groups（ DFO group,positive control group）. An additional six C57 mice of the same age served as negative control group. Mice in the epimedium,astragalus,radix puerariae and compound groups were given via intragastric administration of 120 mg / kg epimediumherb,80 mg / kg milkvetch root,80 mg / kg kudzuvine root,120 mg / kg epimedium herb ＋ 80 mg / kg milkvetch root ＋ 80 mg /kg kudzuvine root,respectively,once a day for thirty consecutive days. A similar regimen of treatment was followed for mice in the DFO group,and for mice in model and control groups which received intramuscular injection of 30 mg / kg deferoxamine and intragastrically 1 ml of normal saline,respectively. The pathological changes on cortex of APP / PS1 double transgenic mouse were investigated by Nissl staining,Bielschowsky staining and transmission electron microscopy. Results： Nissl staining showed that compared with the model group,neurons of the epimedium,milkvetch and kudzuvine groups had a slight increase in number and an attenuation of neuronal swelling. In the compound and DFO groups,cortical neurons were arranged regularly and densely,with the presence of abundant cytoplasmic Nissl bodies,showing attenuated swelling and increased cell number. The modified Bielschowsky staining showed that there was a large amount of senile plaques in the cerebral cortex of mice in AD model group and the number of senile plaques in the epimedium,milkvetch and kudzuvine groups was less than that in the AD model group. Compared with AD model group and single herbal extract-treated groups,the mice in compound and DFO groups showed less number of senile plaques,the ultrastructure of cerebral cortex neurons in mice of each group by transmission electron microscopy showed that the shape of neurons in these two groups was more regular,with neurons showing a little lipofuscin. Conclusion： The compound of epimedium,astragalus and radix puerariae can reduce the senile plaques and repair the neurons injury on the cortex of APP / PS1 AD model.