摘要
目的:研究淫羊藿次苷Ⅱ(ICSⅡ)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、ICSⅡ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,ICSⅡ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ICSⅡ能抑制Aβ沉积、减少神经细胞凋亡,保护脑组织;同时ICSⅡ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ICSⅡ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:ICSⅡ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。
Objective:To investigate the effect of icarisideⅡ(ICSⅡ)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,ICSⅡgroup,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;Aβsedimentation and cell apoptosis in the brain of mice were detected using immunofluorescence histochemistry method.The correlation between the anti-apoptotic effect of ICSⅡand 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 ICSⅡgroup were significantly improved(P<0.01);the fluorescence intensity of Aβand number of positive cleaved caspase-3 cellsin the hippocampus and cortex of mice in the ICSⅡgroup were significantly reduced(P<0.05,P<0.01),indicating that ICSⅡcould inhibit Aβsedimentation,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 inthe hippocampus of mice in the ICSⅡgroup was significantly increased(P<0.05,P<0.01),while the ratio of Bax/Bcl-2 was significantly decreased(P<0.01),indicating that ICSⅡactivated 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:ICSⅡhas 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.
作者
施懿峻
王翠
闻彩名
肖洪贺
李彤
白家鸣
杨静娴
SHI Yi-jun;WANG Cui;WEN Cai-ming;XIAO Hong-he;LI Tong;BAI Jia-ming;YANG Jing-xian(School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116620,China;Department of Neurology,Dalian Municipal Central Hospital,Dalian 116089,China)
出处
《中国现代中药》
CAS
2024年第7期1164-1172,共9页
Modern Chinese Medicine
基金
辽宁省教育厅科学技术研究项目(L201945)。
