藏药七十味珍珠丸改善APP/PS1小鼠学习记忆能力

藏药七十味珍珠丸（ratanasampil，RNSP）可改善大脑氧化应激水平，改善大脑功能，有安神和促进学习记忆的功效，然而RNSP是否可改善阿尔茨海默症（AD）小鼠的学习记忆功能，尚缺乏系统研究。本研究采用APP/PS 1转基因小鼠为研究对象，并随机将其分为实验组和对照组。对实验组进行为期12周的RNSP灌胃给药，对照组进行12周的蒸馏水灌胃，采用Morris水迷宫与开场实验评价小鼠学习记忆能力，比较小鼠体重与相关器官质量，并比较器官质量指数，通过分子生物学检测指标评价小鼠脑内老年斑数量，Aβ生成量及BACE1表达水平。本研究证实，与对照组相比，给药组小鼠定位航行潜伏期明显缩短（22.60±13.26 vs. 46.44±8.41, P<0.01, day 5），穿越平台次数明显增加（1.29±0.37 vs. 0.54±0.29, P<0.01），探洞次数明显增加（32.11±9.85 vs. 20.89±8.78, P<0.05），表明RNSP提高了APP/PS 1小鼠的学习记忆能力和空间探索能力。与对照组相比，给药组小鼠大脑重量及脑质量指数均增高（0.4135±0.0102 vs. 0.3833±0.0254, P<0.05；2.04±0.08 vs. 1.84±0.15, P<0.05），脑内老年斑数量减少（18.70±7.88 vs. 38.83±6.15, P<0.05），Aβ1- 42水平及BACE1表达均显著降低（0.19±0.08 vs. 0.41±0.12, P<0.05; 0.136±0.04 vs. 0.206±0.02, P<0.05），表明RNSP延缓了APP/PS 1小鼠的脑萎缩进程，降低脑内老年斑的形成，下调脑内Aβ1-42水平和BACE1裂解酶的蛋白质表达量。本研究提示，RNSP可改善APP/PS 1小鼠的学习记忆能力，其机制可能和RNSP抑制脑萎缩，降低BACE1蛋白表达以及减少脑内Aβ沉积有关。

Tibetan Medicine RNSP Improves APP/PS1 Mice Learning and Memory Ability

It has been shown that Tibetan medicine ratanasampil (RNSP) can reduce the level of oxidative stress in the brain, improve the function of brain and nerves, and promote the learning and memory ability. However, whether RNSP can improve the learning and memory of mice with Alzheimer’s disease is not clear. In this study, APP/PS 1 transgenic mice were used and randomly divided into experimental group (group AR) and control group (group AC). The experimental or control groups were administrated with RNSP or distil water respectively by intragastrical gavage for 12 weeks. We evaluated the learning and memory ability of mice by Morris water maze test and open field test. Body weight, organ weight, and organ mass index were used to assess developmental status of the mice. The number of senile plaques, production of amyloid beta and expression level of BACE1 in mouse brain were evaluated. This study demonstrated that, compared with the control group, the escape latency of the mice in treatment group was decreased (46.44 ± 8.41 vs. 22.60 ± 13.26, P<0.01, day 5), whereas the numbers of crossing platform (1.29 ±0.37 vs. 0.54 ± 0.29, P<0.01) and exploratory heading in the open field test (32.11 ± 9.85 vs. 20.89 ± 8.78, P<0.05) was increased significantly. These results indicated that RNSP improved the learning and memory ability, and space exploration of APP/PS 1 mice. Compared with the control group, the brain weight (0.4135 ± 0.0102 vs. 0.3833 ± 0.0254, P<0.05) and mass index (2.04 ± 0.08 vs. 1.84 ± 0.15, P<0.05) of the treatment group mice were increased, whereas the number of senile plaques (18.70 ± 7.88 vs. 38.83 ± 6.15, P<0.05) and the levels of Aβ1- 42 (0.19 ± 0.08 vs. 0.41 ± 0.12, P<0.05) and BACE1 (0.136 ± 0.04 vs. 0.206 ± 0.02, P<0.05) in the brain were decreased significantly. These results showed that RNSP delayed the process of brain atrophy, reduced the formation of senile plaques and expression of Aβ1- 42 and BACE1 in the brain of APP/PS 1 mice. These results suggested that RNSP can improve the learning and memory ability of APP/PS 1 mice, and its mechanism may be related to the inhibition of brain atrophy and reduction of the expression of BACE1 protein and the deposition of amyloid beta in the brain.