目的 观察补益脾胃元气类方药人参汤、洗心汤、大补元煎对SAMP8小鼠学习记忆能力和海马区蛋白激酶A（PKA）/细胞外调节激酶（ERK）/磷酸化cAMP反应元件结合蛋白（p-CREB）信号通路的影响，探讨其防治阿尔茨海默病（AD）的作用机制。方法 将3月龄SAMP8小鼠随机分为模型组、安理申组、补益脾胃元气类方药组（人参汤组、大补元煎组、洗心汤组），另以3月龄SAMR1小鼠作为对照组，共6组，连续ig给药10周后进行相关指标检测。采用Morris水迷宫实验观察各组小鼠空间学习记忆能力。免疫组化法检测PKA蛋白表达，免疫荧光法检测ERK、p-CREB蛋白表达。蛋白印迹法检测小鼠海马区PKA、p-CREB、ERK蛋白表达。结果 与模型组比较，补益脾胃元气类方药各组小鼠逃避潜伏期缩短，在目的象限游泳时间及穿越平台次数增加（P<0.05、0.01）；免疫组化结果提示补益脾胃元气类方药各组小鼠海马区PKA蛋白表达量增加（P<0.01）；免疫荧光结果提示补益脾胃元气类方药各组小鼠海马区ERK、p-CREB蛋白表达量增加（P<0.05、0.01）；蛋白印迹实验结果与免疫组化、荧光结果一致。结论 补益脾胃元气类方药对SAMP8小鼠空间学习记忆有明显的改善作用，其机制可能与改善海马区PKA/ERK/p-CREB信号通路有关。

Objective To study the effects of prescriptions including Ginseng Decoction, Xixin Decoction, and Dabuyuan Decoction for tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice, and explore the mechanism in the prevention and treatment of Alzheimer's disease (AD). Methods Three-month-old SAMP8 mice were randomly divided into model group, Donepezil Hydrochloride group, prescription group of Tonifying Spleen and Stomach Yuanqi Prescription (Ginseng, Xixin Decoction, and Dabuyuan Decoction). Moreover, three-month-old SAMR1 mice were recruited as a normal control group, six groups in total. Related indices were detected after 10 weeks continuous gastrogavage. The spatial learning-memory deficit of mice was detected by Morris water maze test. The expression levels of PKA protein in hippocampal region of mice were detected by immunohistochemistry, and the expression levels of ERK and p-CREB protein in hippocampal region of mice were detected by immunofluorescence. The protein expression levels of PKA, ERK, and p-CREB in hippocampus were detected by Western blotting. Results Compared with the model group, the escape latency of the prescription group of tonifying spleen and stomach was decreased (P < 0.05, P < 0.01), while the swimming time and the times of crossing the platform in the target quadrant were increased (P < 0.01). Results of immunohistochemistry showed that the protein expression of PKA was significantly increased and the expression of ERK and p-CREB in hippocampal region was significantly increased (P < 0.05, P < 0.01). The results of Western blotting were consistent with those of immunohistochemistry and immunofluorescence (P < 0.05, P < 0.01). Conclusion The Tonifying Spleen and Stomach Yuanqi Prescription showed obvious improvement on the spatial learning-memory deficit in SAMP8 mice, which might be associated with affecting the PKA/ERK/p-CREB pathway in hippocampal region.

R285.5

陕西省自然科学基础研究计划-重大基础研究项目（2017ZDJC-15）；国家自然科学基金面上项目（81674042）