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

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。

Effect of Forsythiaside on Scopolamine-induced Learning and Memory Impairment in Mice

Objective: To investigate the effect of forsythiaside on scopolamine-induced learning and memory impairment in mice, and explored the possible mechanism. Method: Kunming mice were randomly divided into 4 groups (n=12 per group):normal group, scopolamine model group (3 mg·kg^-1), positive control group (donepezil, 3 mg·kg^-1), and forsythiaside group (200 mg·kg^-1). All groups were administered with drugs by gastric gavage for 2 weeks. On the 14^th day, scopolamine model group, donepezil group and forsythiaside group were intraperitoneally injected with scopolamine (3 mg·kg^-1). 20 min later, the step-down passive avoidance test was performed to evaluate the effect of forsythiaside on AchE and CAMP-extracellular signal-regulated kinase pathway. For another experiment, Kunming mice were randomly divided into 4 groups (n=8 per group):normal group, scopolamine model group (3 mg·kg^-1), positive control group (Vit E, 100 mg·kg^-1), forsythiaside group (200 mg·kg^-1). After 14 days, all mice were beheaded to detect the effect of forsythiaside on superoxide dismutase(SOD), malondialdehyde(MDA) and monoamine oxidase(MAO). Result: Significant effects were observed in the step-down passive avoidance test in the acquisition and consolidation periods. Forsythiaside can increase the reduced safe platform time ratio in the scopolamine group (P<0.05). Forsythiaside can decrease the AchE activity in the cortex and hippocampus, increase the expression of p-ERK in hippocampus (P<0.05), with statistically significant differences compared with model group. Compared with the model group, scopolamine can reduce SOD, MDA and MAO content in cortex and hippocampus (P<0.05). Forsythiaside can significantly increase SOD, MDA and MAO content in cortex and hippocampus, with significant differences compared with scopolamine group (P<0.05). Conclusion: Forsythiaside ameliorated scopolamine-induced learning and memory impairment by modulating AchE activity, cAMP expression and p-ERK and resisting oxidation.