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目的:研究金思维提取物(GEPT)对APPV717I转基因小鼠痴呆早期学习记忆的影响,并进一步探讨其可能的机制。方法:将3月龄的APPV717I转基因小鼠随机分为模型组、多奈哌齐治疗组(0.92mg·kg-1·d-1)、GEPT低、中、高(0.075,0.15,0.3g·kg-1·d-1)剂量组,并以同月龄遗传背景相同的C57BL/6J小鼠作为正常组,每组6只,每天灌胃给药1次。给药4个月后(7月龄)用Morris水迷宫进行行为学测试,用免疫组化方法测定海马CA1区突触相关蛋白Shank1的表达变化,同时用透射电镜观察海马CA1区突触的超微结构变化。结果:行为学检测,GEPT治疗组与模型组相比定位航行实验和空间探索实验均有显著差异(P<0.05)。突触相关蛋白Shank1,模型组小鼠大脑海马CA1区中Shank1阳性细胞总面积以及阳性细胞积分吸光度与正常组相比明显减少,而GEPT治疗组与模型组相比能显著提高Shank1阳性细胞总面积以及阳性细胞积分吸光度(P<0.05)。电镜结果显示,模型组小鼠可见突触数量减少,突触间隙增宽,突触界面曲率下降,突触后致密区厚度减小,GEPT治疗组能剂量依赖性的对突触损害起到修复作用。结论:GEPT能通过修复突触损伤以及提高Shank1蛋白的表达进而改善APPV717I转基因小鼠痴呆早期的学习记忆能力。
Objective: To investigate the effect of GST on the early learning and memory of APPV717I transgenic mice and to explore its possible mechanism. Methods: Three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil treatment group (0.92 mg · kg -1 · d -1), low, medium and high GEPT (0.075,0.15,0.3 g · kg -1 · D-1) dose group. C57BL / 6J mice with the same genetic background at the same age were used as normal group, with 6 rats in each group. Behavioral tests were performed in Morris water maze 4 months after drug administration. Shank1 protein expression in hippocampal CA1 region was detected by immunohistochemistry. Meanwhile, transmission electron microscopy Microstructure changes. Results: Compared with the model group, the behavioral tests showed that the GEPT treatment group had significant difference (P <0.05) in space navigation experiment and space exploration experiment. Compared with the normal group, the total area of Shank1 positive cells and the positive cell integral absorbance of the synaptic-related protein Shank1 in the hippocampal CA1 region of the model group mice were significantly decreased, while the total area of the Shank1 positive cells in the GEPT treatment group was significantly increased As well as positive cell integral absorbance (P <0.05). Electron microscopy showed that in the model group, the number of synapses decreased, the synaptic gap widened, the curvature of the synaptic interface decreased and the thickness of the post-synaptic densified zone decreased. GEPT treatment group could repair the synaptic damage dose-dependently effect. Conclusion: GEPT can improve the learning and memory ability of APPV717I transgenic mice in early stage of dementia by repairing the synaptic damage and increasing the expression of Shank1 protein.