【摘要】 目的:通过观察远志皂苷加β-细辛醚对APP/PS1双转基因小鼠海马超微结构、行为学,以及蛋白激酶B （proteinkinase B,AKt）和糖原合成激酶3β（glycogen synthase kinase 3β,GSK-3β）表达的影响,探讨"化痰开窍"法防治阿尔茨海默病（AD）的作用机制。方法:以3个月龄的APP/PS1双转基因小鼠为研究对象,设为模型组、药物组经远志皂苷+β-细辛醚(74 mg·kg^-1·d^-1)处理,正常对照组为3个月龄的C57BL/6小鼠。采用透射电镜观察小鼠海马超微结构;采用Morris水迷宫法和新物体识别实验检测药物对小鼠学习记忆能力的改善;应用免疫组化法检测Akt和GSK-3β的蛋白表达。结果:远志皂苷联合β-细辛醚可以改善APP/PS1双转基因小鼠的空间和非空间记忆功能,逆转APP/PS1双转基因小鼠海马神经元超微形态,上调p-Akt和p-GSK-3β的蛋白表达（P <0. 05）。结论:远志汤的"化痰开窍"防治AD的药理效能,可能是通过调控Akt/GSK-3β通路实现的。更多还原

【Abstract】 Objective: To observe the effects of Tenuigenin and β-asarone on the regulation of Akt and GSK-3β,ultrastructure and praxiology in APP/PS1 double transgenic mice,and explore the mechanism of prevention and treatment of Alzheimer disease（AD） with the method of "dissipating phlegm for resuscitation". Methods:Three-month-old APP/PS1 double transgenic mice were divided into model group,high dose β-asarone and Tenuigenin group,medium does β-asarone and Tenuigenin group and low dose β-asarone and Tenuigenin group(74 mg·kg^-1·d^-1). C57 BL/6 mice of the same age were selected as the control group. Transmission electron microscope was used to observe the ultrastructure of the mice. Immunohistochemical test was performed to evaluate the expressions of glycogen synthase kinase-3β（GSK-3β）,phosphorylated GSK-3β,Akt and p-Akt. Results:β-asarone and Tenuigenin treatment significantly ameliorated the cognitive deficits of APP/PS1 double transgenic mice,improved the ultrastructure of hippocampal neurons in APP/PS1 mice,suppressed the activation of GSK-3β,and enhanced the activation of Akt. Conclusion: The pharmacological effect of Polygala Decoction,dissipating phlegm for resuscitation,in prevention and treatment of AD may be achieved by regulating the Akt/GSK-3 beta pathway.更多还原