地黄饮子有效成分SA调节神经递质改善AD小鼠认知功能机制研究-现代医学

地黄饮子有效成分SA调节神经递质改善AD小鼠认知功能机制研究

单位：1. 黑龙江中医药大学基础医学院, 黑龙江哈尔滨 150040;
2. 黑龙江省中医基础理论研究重点实验室, 黑龙江哈尔滨 150040

分类号：R741.05

出版年·卷·期（页码）：2026·54·第一期（26-33）

摘要：

目的：旨在系统阐明中药复方地黄饮子有效成分五味子醇甲(SA)通过调节神经递质水平改善阿尔茨海默症(AD)小鼠认知功能的作用机制。方法：24只雄性6月龄APP/PS1双转基因小鼠随机分为模型组、西药组(盐酸多奈哌齐)和地黄饮子组(中药复方地黄饮子)，每组8只；另8只同月龄雄性C57BL6小鼠作为空白组。连续灌胃4周后对各组小鼠进行Morris水迷宫实验；利用微透析技术提取脑脊液，UPLC-ESI-MS/MS检测不同时段小鼠脑内谷氨酸(Glu)、乙酰胆碱(Ach)和SA含量动态变化；探讨SA与Glu、Ach的动态关系。结果：Morris水迷宫实验中，第2天开始所有组小鼠潜伏期时长均显示逐步缩短，且空白组、西药组及地黄饮子组均显著短于模型组(P<0.05)；空间探索结果显示，与模型组相比，地黄饮子组与西药组穿越平台次数和目标象限活动路程均明显增加(P<0.05)。Ach含量结果显示，给药第4周，与空白组相比，模型组、西药组及地黄饮子组Ach含量显著下降，但与模型组相比，地黄饮子组和西药组Ach的含量升高(P<0.01)。Glu含量结果显示，地黄饮子组Glu含量前期呈缓慢上升趋势，灌胃2周后呈下降趋势(P<0.05)。SA含量结果显示，灌胃4周后地黄饮子组SA含量开始升高，第4周内SA含量整体高于第1周。动态关系结果显示，Ach含量随SA的含量升高呈现波动性递增特征(P<0.01)；Glu含量呈现先升高后下降的趋势，在第3周开始Glu含量显著下降(P<0.01)，与SA的含量呈现相反的变化。结论：地黄饮子有效成分SA可降低AD小鼠海马内Glu含量，提高Ach含量，改善其学习记忆能力。

Objective: To systematically elucidate the mechanism by which schisandrin A(SA), an active component of the traditional Chinese medicine compound Dihuang Yinzi decoction, improves cognitive function in Alzheimer's disease(AD) mice by regulating neurotransmitter levels. Methods: Twenty-four 6-month-old male APP/PS1 double-transgenic mice were randomly divided into three groups: model group, western medicine group(donepezil hydrochloride), and Dihuang Yinzi decoction group(n=8 per group). Eight age-matched male C57BL/6 mice served as the blank control group. After 4 weeks of continuous intragastric administration, the Morris water maze test was performed to evaluate cognitive function. Microdialysis was used to collect cerebrospinal fluid, and ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry(UPLC-ESI-MS/MS) was employed to detect the dynamic changes in the levels of glutamate(Glu), acetylcholine(Ach), and SA in the mouse brain at different time points. The dynamic relationships between SA and Glu/Ach were further analyzed. Results: In the Morris water maze test, the escape latency of mice in all groups gradually shortened from day 2, with the blank control group, western medicine group and Dihuang Yinzi decoction group showing significantly shorter latency than the model group(P<0.05). Spatial probe test results indicated that compared with the model group, both the Dihuang Yinzi decoction group and western medicine group exhibited a marked increase in the number of platform crossings and the distance traveled in the target quadrant(P<0.05). For Ach levels, after 4 weeks of administration, the model group, western medicine group and Dihuang Yinzi decoction group showed a significant decrease in Ach content compared with the blank control group; however, Ach levels in the Dihuang Yinzi decoction group and western medicine group were significantly higher than those in the model group(P<0.01). Regarding Glu levels, the Dihuang Yinzi decoction group showed a slow upward trend in the early stage, followed by a significant decrease after 2 weeks of intragastric administration(P<0.05). For SA levels, the Dihuang Yinzi decoction group exhibited an increase starting from 4 weeks of administration, with overall SA levels in the 4th week being higher than those in the 1st week. Dynamic relationship analysis revealed that Ach levels showed a fluctuating increasing trend with the elevation of SA levels(P<0.01), while Glu levels first increased and then decreased, with a significant decline starting from the 3rd week(P<0.01), exhibiting an opposite trend to SA levels. Conclusion: SA, an active component of Dihuang Yinzi decoction, can reduce hippocampal Glu levels, increase Ach levels, and improve learning and memory abilities in AD mice.

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