连翘酯苷对东莨菪碱模型小鼠学习记忆的影响及其机制研究

发布时间：2019-06-29 18:26

【摘要】：目的:研究连翘酯苷对东莨菪碱模型小鼠学习记忆的影响,并探讨其作用机制,为连翘酯苷抗阿尔茨海默病研究提供数据支撑。方法:昆明种小鼠,随机分为4组,分别为正常组,东莨菪碱模型组,多奈哌齐组(3 mg·kg-1)和连翘酯苷(200 mg·kg-1)组,每组12只。各组连续给药14 d。给药第14天,东莨菪碱模型组、多奈哌齐组和连翘酯苷组给予东莨菪碱(3 mg·kg-1),腹腔注射。20 min后,进行跳台实验。同时,观察连翘酯苷对乙酰胆碱酯酶(Ach E)和环磷酸腺苷-细胞外信号调节激酶通路的影响。另设一批实验,昆明种小鼠分为4组,分别为正常组,东莨菪碱模型组,维生素E组(100 mg·kg-1)和连翘酯苷(200 mg·kg-1)组,给药14 d后,断头处死动物,检测连翘酯苷对东莨菪碱模型超氧化物歧化酶(SOD),丙二醛(MDA),单胺氧化酶(MAO)的影响。结果:跳台实验获得期和巩固期,东莨菪碱模型组与正常组比较,安全期时间比率显著下降(P0.05),连翘酯苷显著增加安全期时间比率(P0.05)。连翘酯苷显著降低东莨菪碱模型小鼠大脑皮层和海马Ach E活性(P0.05)。连翘酯苷显著升高东莨菪碱模型小鼠海马P-ERK含量,与东莨菪碱组比较,具有显著性差异(P0.05)。同时,东莨菪碱组与正常组比较,显著降低小鼠大脑皮层和海马SOD活性、升高MDA含量、升高MAO活性(P0.05)。连翘酯苷能显著升高小鼠大脑皮层和海马SOD活性、降低MDA含量和MAO活性,与东莨菪碱组比较,具有显著性差异(P0.05)。结论:连翘酯苷可提高东莨菪碱模型小鼠的学习记忆能力,其机制可能与抑制模型小鼠大脑皮层Ach E活性,促进环磷酸腺苷(c AMP)表达,活化细胞外信号调节激酶(ERK)及抗氧化有关。
[Abstract]:Aim: to study the effect of phillyrin on learning and memory of scopolamine model mice and to explore its mechanism, so as to provide data support for the study of forsythyl glycoside against Alzheimer's disease. Methods: Kunming mice were randomly divided into 4 groups: normal group, scopolamine model group, donepezil group (3 mg kg-1) and forsythrin (200 mg kg-1) group, with 12 mice in each group. Each group was given continuously for 14 days. On the 14th day of administration, scopolamine model group, Donepazil group and forsythyl glycoside group were given scopolamine (3 mg kg-1). After 20 min injection, the platform test was carried out. At the same time, the effects of phillyrin on acetylcholinesterase (Ach E) and cyclic adenosine monophosphate extracellular signal-regulated kinase pathway were observed. In addition, Kunming mice were divided into four groups: normal group, scopolamine model group, vitamin E group (100 mg kg-1) and forsythol glycoside (200 mg kg-1) group. After 14 days of administration, the animals were decapitated and the effects of forsythyl glycosides on (SOD), malondialdehyde (MDA), monoamine oxidase (MAO) in scopolamine model were detected. Results: compared with the normal group, the safe period time ratio of scopolamine model group decreased significantly (P 0.05), and forsythyl glycoside significantly increased the safety period time ratio (P 0.05). Phillyrin significantly decreased Ach E activity in cerebral cortex and hippocampus of scopolamine model mice (P 0.05). Phillyrin significantly increased the content of P-ERK in hippocampus of scopolamine model mice, which was significantly different from that of scopolamine group (P 0.05). At the same time, compared with the normal group, scopolamine group significantly decreased SOD activity, increased MDA content and increased MAO activity in cerebral cortex and hippocampus of mice (P 0.05). Phillyrin significantly increased SOD activity and decreased MDA content and MAO activity in cerebral cortex and hippocampus of mice, which were significantly different from those in scopolamine group (P 0.05). Conclusion: phillyrin can improve the learning and memory ability of scopolamine model mice, and its mechanism may be related to the inhibition of Ach E activity in cerebral cortex of model mice, the promotion of cyclic adenosine monophosphate (c AMP) expression, the activation of extracellular signal-regulated kinase (ERK) and antioxidant activity.
【作者单位】：山东中医药大学附属医院;北京协和医学院比较医学中心中国医学科学院医学实验动物研究所卫生部人类疾病比较医学重点实验室国家中医药管理局人类动物模型三级实验室;中国医学科学院药用植物研究所北京协和医学院药理毒理中心;
【基金】：全军医学科技“十二五”科研项目(BWS11J052) 对欧科技合作专项-保健品风险效益评估合作研究项目(1108)
【分类号】：R285.5;R-332

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