桂枝汤苯丙烯类化合物对APP转基因AD小鼠学习记忆障碍的影响

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(P0.05);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(P0.01)和站台象限时间比率(P0.05)。同时,PCGZT可以降低AD小鼠脑MDA含量(P0.05)和血清中MMP-9含量(P0.05),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。

Effects of Phenylallyl Compounds from Guizhi Tang on Learning and Memory Impairment in APP Transgenic AD Mice

Objective: To study the effects and possible mechanisms of phenylallyl compounds from Guizhi Tang (PCGZT) on learning and memory impairment in APP transgenic Alzheimer''s disease(AD) mice. Method: Three-month-old APP transgenic AD mice were randomly divided into model group, aspirin group, piracetam group, huperzine-A group, PCGZT groups (high, medium and low doses), and normal control group (C57BL/6J mice) according to their weight, with 10 in each group. These mice were intragastrically administered with aspirin (20 mg·kg^-1·d^-1), piracetam (600 mg·kg^-1·d^-1), huperzine-A (0.3 mg·kg^-1·d^-1) and different doses of PCGZT (64.4, 32.2, 16.1 mg·kg^-1·d^-1) respectively for consecutively 5 months. Model groups and normal control group were treated with 0.5%carboxymethy cellulose sodium (CMC-Na). The abilities of learning and memory of mice were detected by step down test and morris water maze test. The contents of matrix metalloprotein-2 (MMP-2) and matrix metalloprotein-9 (MMP-9) in the blood serum and malondialdehyde (MDA) activity in brain tissues were measured. Result: Compared with model group, PCGZT can reduce latent reaction time (P < 0.05), error frequency (P < 0.01) and total time of error period (P < 0.01), improve total time of safety period (P < 0.05) of APP transgenic AD mice in step down test, low dose group of PCGZT can improve percentage of the platform quadrant distance (P < 0.01) and the platform quadrant time (P < 0.05) in morris water maze test. At the same time, PCGZT can decrease MDA and MMP-2 contents in the serum (P < 0.05). Conclusion: PCGZT can dramatically alleviate the learning and memory impairment of APP transgenic AD mice, and its mechanism may involve multiple drug targets.