目的 研究补益脾胃元气方药人参、大补元煎、洗心汤对快速老化痴呆模型（SAMP8）小鼠空间学习记忆能力、海马区形态功能和皮层胆碱能系统的影响，探讨其治疗阿尔茨海默病的可能作用机制。方法 3月龄雄性SAMP8小鼠随机分为模型组、盐酸多奈哌齐组、人参组、洗心汤组、大补元煎组，以雄性抗快速老化型（SAMR1）小鼠为对照组。除对照组和模型组ig蒸馏水外，其余各组ig药物（10 mL/kg），1次/d，连续3个月。实验结束后采用Morris水迷宫实验检测小鼠空间学习记忆能力，透射电镜观察小鼠海马CA3区突触超微结构，免疫组化法检测CA1区神经元密度、脑组织β淀粉样蛋白（Aβ）水平，生物化学法检测海马胆碱乙酰基转移酶（ChAT）和乙酰胆碱酯酶（AChE）的活性。结果 补益脾胃元气方药各组小鼠逃避潜伏期平均值明显下降，在目的象限游泳时间、穿过平台次数显著增加（P<0.05、0.01）；各组小鼠Aβ阳性细胞数目显著降低（P<0.05、0.01），神经元特异核蛋白（NueN）阳性细胞密度有上升趋势，但无显著差异；各组小鼠ChAT活性升高（P<0.05、0.01），人参、洗心汤组小鼠AChE活性降低（P<0.05）。结论 补益脾胃元气方药对SAMP8小鼠空间识别和学习记忆能力有明显改善作用，其机制可能与影响小鼠海马突触结构、促进海马神经元修复、降低小鼠脑内Aβ表达、调节海马胆碱能系统有关。

Objective To study the effect of Tonifying Spleen and Stomach Yuanqi Prescriptions including ginseng, Dabuyuan Decoction and Xixin Decoction on spatial learning and memory ability, hippocampal morphological function and cortical cholinergic system in rapidly aging dementia model mice (SAMP8), and investigate the possible mechanism on treating Alzheimer's disease. Methods Male SAMP8 mice aged three months were randomly divided into model group, donepezil group, ginseng group, Xixin Decoction group and Dabuyuan Decoction group. Male anti-aging mice (SAMR1) were used as control group. In addition to control 3 months). The spatial learning and memory ability of mice was observed by Morris water maze test; The synaptic ultrastructure of hippocampal CA3 region was observed by transmission electron microscope; The density of neurons in CA1 area and the level of Aβ in brain tissue were detected by immunohistochemistry; The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus were detected by biochemical method. Results The average escape latency of mice treated with Tonifying Spleen and Stomach Yuanqi Prescriptions was decreased, the swimming time and the number of passing through the platform were increased significantly (P < 0.05, 0.01). The number of Aβ positive cells were significantly decreased (P < 0.05, 0.01), the density of NueN positive cells had no significant difference. The level of CHAT activity was increased (P < 0.05, 0.01), and the level of AChE activity was decreased (P < 0.05). Conclusion The effect of Tonifying Spleen and Stomach Yuanqi prescriptions improve the spatial recognition and learning and memory abilities in SAMP8 mice, of which mechanism may be related to affect the synaptic structure of hippocampus, promote the repair of hippocampal neurons, reduce the expression of Aβ in mouse brain, and regulate the cholinergic system in cortex.

R285.5

国家自然科学基金项目（81674042，81373703）；陕西省自然科学基础研究计划-重大基础研究项目（2017ZDJC-15）；陕西省“特支计划”人才项目（141019040）；陕西中医药大学学科创新团队项目（2019-QN05）