远志汤有效成分对APP/PS1 小鼠氧化损伤的保护作用机制研究

Study on protective effect of effective components of Polygala Decoction on oxidative damage in APP/PS1 double transgenic mice

摘要:

目的 通过观察远志汤有效成分即β- 细辛醚+ 远志皂苷（TEN）对APP/PS1 双转基因小鼠磷脂酰肌醇3- 激酶（PI3K）/ 蛋白激酶B（Akt）/ 糖原合成激酶3β（GSK-3β）信号通路的调控，探讨远志汤防治阿尔茨海默病（AD）的作用机制。方法 将3 月龄APP/PS1 双转基因小鼠分为模型组、盐酸多奈哌齐组（0.33 mg/kg·d）、β- 细辛醚+TEN 低、中和高剂量组[18.5、37.0 和74.0 mg/（kg·d）]，选同月龄C57BL/6 小鼠为空白对照组，采用Morris 水迷宫法和新物体识别实验检测小鼠的学习记忆能力，采用分光光度法检测超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、过氧化氢酶（CAT）活性，以及丙二醛（MDA）含量。采用Western blot 检测GSK-3β、Akt，以及两者磷酸化蛋白表达。结果 β- 细辛醚协同TEN 可增强APP/PS1 双转基因小鼠的学习记忆功能，同时还能升高SOD、CAT 和GSH-PX 的活性，降低MDA 含量，诱导Akt 的蛋白表达，抑制GSK-3β 的表达。结论 远志汤有效成分即β- 细辛醚+TEN 可通过调控PI3K/Akt/GSK-3β 信号通路，对APP/PS1 双转基因小鼠氧化应激损伤发挥保护作用。

Abstract:

Objective To observe the regulative effect of β-asarone and Tenuigenin on the PI3K/Akt/GSK-3β signaling pathway in APP/PS1 double transgenic mice, to explore the mechanism of Polygala Decoction in prevention and treatment of Alzheimer’s disease. Methods Three-month-old APP/PS1 double transgenic mice were divided into model group, Donepezil hydrochloride group (0.33 mg/kg·d), high-dose β-asarone and Tenuigenin group, medium-does β-asarone and Tenuigenin group and low-dose β-asarone and Tenuigenin group (18.5, 37.0 and 74.0 mg/kg·d). C57BL/6 mice of the same age were selected as the control group. Morris water maze test and new object recongnition task were used to measure the spatial learning and memory ability. Spectrophotometer was used to detect the activity of SOD, catalase (CAT) and glutathione peroxidase (GSH-PX) and the content of MDA. Western blot was performed to evaluate the expressions of glycogen synthase kinase-3β (GSK-3β), p-GSK-3β, Akt and p-Akt. Results β-asarone and Tenuigenin significantly ameliorated the cognitive defect of APP/PS1 double transgenic mice, increased the activity of SOD, CAT and GSH-PX, while decreased the content of MDA, suppressed the activation of GSK-3β and enhanced the activation of Akt. Conclusions β-asarone and Tenuigenin can inhibit the oxidative stress of brain tissue, and exhibit positive therapeutic effect on Alzheimer’s disease by regulating the activity of the PI3K/Akt/GSK-3β signaling pathway.