摘要
目的:考察补骨脂提取物对APP/PS1转基因小鼠学习记忆能力的改善作用及其与雌激素受体β(ERβ)/细胞外调节蛋白激酶(ERK)信号通路的内在联系。方法:将60只3月龄雄性APP/PS1小鼠随机分为模型组、盐酸多奈哌齐(0.65 mg/kg)组、抗脑衰胶囊(0.585 g/kg)组及补骨脂提取物(0.5 g/kg)组,另将15只同背景、同月龄雄性C57小鼠作为正常对照组。新物体识别实验观察各组小鼠新物体识别指数;水迷宫实验观察各组小鼠穿越平台次数及靶象限停留时间;透射电镜法、HE染色法观察小鼠海马CA3区神经元形态;免疫组化法检测小鼠海马CA3区ERα、ERβ表达;Western Blot检测海马中ERβ蛋白表达及p-ERK/ERK水平。结果:与正常对照组比较,模型组小鼠新物体识别指数显著降低,定位航行实验潜伏期显著延长,穿越平台次数及靶象限停留时间显著减少(P<0.05或P<0.01),神经元核膜较模糊,细胞质不丰富,海马ERα、ERβ蛋白表达及p-ERK/ERK水平显著降低(P<0.01)。与模型组比较,各给药组新物体识别指数显著升高,定位航行实验潜伏期显著缩短,穿越平台次数及靶象限停留时间显著增加(P<0.05或P<0.01),神经元核膜较清晰,细胞质较丰富,抗脑衰胶囊组及补骨脂提取物组海马ERα、ERβ蛋白表达及p-ERK/ERK水平显著升高(P<0.01)。结论:补骨脂提取物改善APP/PS1小鼠空间学习记忆障碍的机制可能与ERβ/ERK信号通路有关。
Objective:To investigate the improvement of learning and memory ability of Psoraleae Fructus extract in APP/PS1 transgenic mice and its internal relationship with estrogen receptorβ(ERβ)/extracellular regulated protein kinase(ERK)signaling pathway.Methods:Sixty 3-month-old male APP/PS1 mice were randomly divided into model group,donepezil hydrochloride(0.65 mg/kg)group,anti-brain failure capsule(0.585 g/kg)group and Psoraleae Fructus extract group(0.5 g/kg),and 15 male C57 mice with the same background and age were used as normal control group.New object recognition experiment was performed to observe the new object recognition index,Morris water maze test was used to observe the times of crossing the platform and the stay time of the target quadrant of each group mice.The morphology of neurons in hippocampal CA3 region of mice was observed by transmission electron microscopy and HE staining.The expression of ERαprotein and ERβin hippocampal CA3 region of mice were detected by immunohistochemistry.The expression of ERβprotein and the level of p-ERK/ERK in hippocampus were detected by Western Blot.Results:Compared with normal control group,the new object recognition index of model group was significantly decreased,the incubation period of the positioning navigation experiment was significantly prolonged,and the number of crossing platform and the retention time of target quadrant were significantly decreased(P<0.05 or P<0.01),the nuclear membrane of neuron was blurred,the cytoplasm was not rich,the protein expressions of ERα,ERβand the level of p-ERK/ERK in hippocampus was significantly decreased(P<0.01).Compared with model group,the new object recognition index was significantly,increased the incubation period of the positioning navigation experiment was significanty shortened,the number of platform crossing and the residence time of target quadrant were significantly increased(P<0.05 or P<0.01),the nuclear membrane of neuron was clearer,the cytoplasm was richer.The protein expressions of ERα,ERβand the level of p-ERK/ERK in hippocampus of anti-brain failure capsule group and Psoraleae Fructus extract group were significantly increased(P<0.01).Conclusion:The mechanism of Psoraleae Fructus extract improving spatial learning and memory disorders in APP/PS1 mice may be related to ERβ/ERK signaling pathway.
作者
武凤
刘俊岑
徐红丹
胡晶
徐艳明
张宁
刘斌
WU Feng;LIU Jun-cen;XU Hong-dan;HU Jing;XU Yan-ming;ZHANG Ning;LIU Bin(School of Basic Medicine,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;College of Pharmacy,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Jiamusi College,Heilongjiang University of Traditional Chinese Medicine,Jiamusi 154007,China;Wuxi Higher Vocational and Technical School of Health,Wuxi 214028,China)
出处
《中药材》
CAS
北大核心
2022年第7期1699-1704,共6页
Journal of Chinese Medicinal Materials
基金
国家自然科学基金面上项目(82174007)
中央支持地方高校改革发展资金(青年骨干)
黑龙江中医药大学优秀创新人才支持计划(2018RCD19)
国家自然科学基金青年项目(82003975)
无锡市卫生健康委科研项目(M202170)
黑龙江省中医药管理局科研课题(ZHY202087)
黑龙江省卫生健康委科研课题(2020-301)
作者简介
武凤(1998-),女,在读硕士研究生,专业方向:中医药防治老年性疾病的研究,Tel:18846776908,E-mail:2313473249@qq.com;通讯作者:张宁,Tel:0454-6050350,E-mail:zhangning0454@163.com。
