淫羊藿次苷Ⅱ调控PI3K/Akt信号通路对阿尔茨海默病小鼠学习记忆能力的影响
Effect of Icariside Ⅱ on Learning and Memory Abilities of Mice with Alzheimer's Disease via regulating PI3K/Akt Signaling Pathway
施懿峻 1王翠 2闻彩名 1肖洪贺 1李彤 1白家鸣 1杨静娴1
作者信息
- 1. 辽宁中医药大学 药学院,辽宁 大连 116620
- 2. 大连市中心医院 神经内科,辽宁 大连 116089
- 折叠
摘要
目的:研究淫羊藿次苷Ⅱ(ICS Ⅱ)对阿尔茨海默病(AD)模型小鼠学习和记忆能力的影响及其分子机制.方法:将 7 月龄APP/PS1 双转基因小鼠随机分为模型组、ICS Ⅱ组和阳性对照药组,每日灌胃给药 1 次,连续 30 d.用Morris水迷宫与筑巢实验检测小鼠学习记忆和生活能力;用免疫荧光化学法检测脑内β淀粉样蛋白(Aβ)沉积与细胞凋亡情况;用蛋白质免疫印迹法(Western blot)探究其抗凋亡作用与磷脂腺肌醇 3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的相关性.结果:与模型组比较,ICS Ⅱ组小鼠的学习记忆及生活能力都明显提高(P<0.01),其海马与皮层的Aβ荧光强度和裂解的半胱氨酸-天冬氨酸蛋白酶-3(cleaved Caspase-3)阳性细胞数均明显降低(P<0.05,P<0.01),说明ICS Ⅱ能抑制Aβ沉积、减少神经细胞凋亡,保护脑组织;同时ICS Ⅱ组小鼠海马PI3K蛋白质表达水平和p-Akt/Akt显著升高(P<0.05,P<0.01),而Bax/Bcl-2 明显降低(P<0.01),说明ICS Ⅱ抗凋亡作用的机制与激活海马PI3K/Akt信号通路,降低促凋亡蛋白、提高抗凋亡蛋白的表达水平有关.结论:ICS Ⅱ对AD小鼠脑内神经细胞有明显的保护作用,能改善小鼠的认知功能,其机制可能与激活海马PI3K/Akt信号通路有关.
Abstract
Objective:To investigate the effect of icariside Ⅱ(ICS Ⅱ)on the learning and memory abilities of mice with Alzheimer's disease(AD)and its molecular mechanism.Methods:7-month-old APP/PS1 double-transgenic mice were randomly divided into the model group,ICS Ⅱ group,and positive control group,which were administered by gavage once a day for 30 days.Morris water maze and nesting experiment were used to test the learning,memory,and living abilities of mice;Aβ sedimentation and cell apoptosis in the brain of mice were detected using immunofluorescence histochemistry method.The correlation between the anti-apoptotic effect of ICS Ⅱ and the PI3K/Akt signaling pathway was studied using Western Blot.Results:Compared with the model group,the learning,memory,and living abilities of mice in the ICS Ⅱgroup were significantly improved(P<0.01);the fluorescence intensity of Aβ and number of positive cleaved caspase-3 cells in the hippocampus and cortex of mice in the ICS Ⅱ group were significantly reduced(P<0.05,P<0.01),indicating that ICS Ⅱ could inhibit Aβ sedimentation,reduce neuronal cell apoptosis,and thereby protect the brain tissue.At the same time,the protein expression of PI3K and ratio of p-Akt/Akt in the hippocampus of mice in the ICS Ⅱ group was significantly increased(P<0.05,P<0.01),while the ratio of Bax/Bcl-2 was significantly decreased(P<0.01),indicating that ICS Ⅱactivated the PI3K/Akt signaling pathway,inhibited expression of pro-apoptotic proteins,and increased the expression of anti-apoptotic proteins,thus exerting an anti-apoptotic effect.Conclusion:ICS Ⅱ has a significant neuroprotective effect on the brain of mice with AD;it improves the cognitive ability of the mice obviously,and the mechanism may be related to the activation of the PI3K/Akt signaling pathway.
关键词
淫羊藿次苷Ⅱ/阿尔茨海默病/神经细胞凋亡/磷脂腺肌醇3-激酶/蛋白激酶B信号通路Key words
icariside Ⅱ/Alzheimer's disease/neuronal cell apoptosis/PI3K/Akt signaling pathway引用本文复制引用
基金项目
辽宁省教育厅科学技术研究项目(L201945)
出版年
2024
国家科技期刊平台
NSTL
万方数据