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目的:探讨桂枝汤苯丙烯类化合物(PCGZT)对APP转基因阿尔茨海默病(AD)小鼠模型记忆障碍影响及其部分作用机制。方法:按体重随机将3月龄APP695V717转基因小鼠随机分为模型组,阿司匹林组(20 mg·kg-1·d-1),脑复康组(600 mg·kg-1·d-1),石杉碱甲组(0.3 mg·kg-1·d-1)和PCGZT大、中、小剂量(64.4,32.2,16.1 mg·kg-1·d-1)组,每组10只;另取C57BL/6J小鼠10只作为空白组。各组小鼠每天给药1次,约10月龄时,进行Morris水迷宫实验和跳台实验,测定小鼠脑组织丙二醛(MDA)含量,血清中基质金属蛋白酶-2(MMP-2)和MMP-9含量。结果:与模型组比较,PCGZT可以减少APP转基因AD小鼠跳台反应时间,降低错误期总时间和错误次数,提高安全期总时间(P<0.05);PCGZT小剂量组提高APP转基因AD小鼠在Morris迷宫实验中站台象限路程比率(P<0.01)和站台象限时间比率(P<0.05)。同时,PCGZT可以降低AD小鼠脑MDA含量(P<0.05)和血清中MMP-9含量(P<0.05),对MMP-2含量无影响。结论:PCGZT能够明显改善APP转基因AD小鼠学习记忆障碍,其作用机制可能涉及多个药物靶点。
OBJECTIVE: To investigate the effect of Guizhi Tang benzene-propylene compound (PCGZT) on memory impairment in APP transgenic mouse model of Alzheimer’s disease (AD) and its partial mechanism. Methods: Three-month-old APP695V717 transgenic mice were randomly divided into model group, aspirin group (20 mg · kg -1 · d-1) and naofukang group (600 mg · kg -1 · d -1) , Huperzine A group (0.3 mg · kg -1 · d -1) and PCGZT groups (10 mg / kg · d -1) Ten C57BL / 6J mice were used as blank group. The mice in each group were given once a day, and at about 10 months of age, Morris water maze test and platform jumping test were performed to determine the content of malondialdehyde (MDA), the level of matrix metalloproteinase-2 (MMP-2) And MMP-9 content. Results: Compared with the model group, PCGZT could reduce the jump reaction time, reduce the total time and number of mistakes in APP transgenic mice, and increase the total safety period (P <0.05); PCGZT low dose group increased APP transgenic mice The station quadrant distance (P <0.01) and station quadrant time ratio (P <0.05) in the Morris maze experiment. Meanwhile, PCGZT could reduce the content of MDA in brain (P <0.05) and the level of MMP-9 in serum (P <0.05), but had no effect on the content of MMP-2. Conclusion: PCGZT can significantly improve the learning and memory impairment in APP transgenic AD mice. Its mechanism may involve multiple drug targets.