Abstract: Objective　To observe the behavioral characteristics of male 5×FAD mice and intervention effect of Ditan Tang.Methods　Positive mice were screened through tail gene identification, and their learning and memory abilities were evaluated by Barnes maze test(BMT) and novel object recognition (NOR) test. The anxiety status of mice was evaluated by open field test (OFT) and elevated plus maze (EPM) test. The depression status of mice was evaluated by sucrose preference test(SPT), tail suspension test (TST), and forced swimming test (FST). The social ability of mice was evaluated by three-chamber social preference test(TCSP). Observe the intervention effect of Ditan Tang on the behavior of mice of different ages.Results　There was no significant difference in the general condition between 5×FAD mice and C57/BL6 mice. Compared with control group, in BMT, 4, 8, and 12 months’ old 5 × FAD mice showed varying degrees of reduction in the number of correct hole explorations (P<0.05, P<0.01) and in the correct quadrant dwell time (P<0.01). In NOR test, the cognitive coefficient of 4, 8, and 12 months’ old 5×FAD mice decreased to varying degrees (P<0.05).In OFT, the total activity distance, central area dwell time, and upright exploration frequency of 4, 8, and 12 months’ old 5×FAD mice were reduced to varying degrees (P<0.01). In EMP test, the open arm dwell time and downward exploration frequency of 4, 8, and 12 months’ old 5×FAD mice decreased to varying degrees (P<0.01), while the closed arm dwell time increased to varying degrees (P<0.01). In TST and FST, the immobility time of 4, 8, and 12 months’ old 5×FAD mice increased to varying degrees (P<0.01). In SPT, the sucrose skewness of 4, 8, and 12 months’ old 5×FAD mice was reduced to varying degrees (P<0.01). Ditan Tang significantly improved the above indicators in 4-month-old 5 × FAD mice, and partially improve some indicators in 8- and 12-month old 5×FAD mice.Conclusion Ditan Tang can effectively improve the anxiety and depression status of 4-month-old male 5×FAD mice.It provides theoretical basis for clinical application.

Key words: Alzheimer disease, β-amyloid protein, anxiety, depression, Ditan Tang

摘要： 目的　观察雄性5×FAD小鼠的行为学特征及涤痰汤的干预作用。方法　通过鼠尾基因鉴定筛选出阳性小 鼠,采用巴恩斯迷宫实验(BMT)、新物体识别(NOR)实验评价小鼠学习记忆能力;采用旷场实验(OFT)、高架十字 迷宫(EPM)实验评价小鼠焦虑状态;采用糖水偏好实验(SPT)、悬尾实验(TST)、强迫游泳实验(FST)评价小鼠抑 郁状态;采用三箱社交实验(TCSP)评价小鼠社交能力。观察涤痰汤对不同月龄小鼠行为学的干预作用。 结果　5×FAD 小鼠的一般情况与C57/BL6小鼠无明显差异。与对照组小鼠比较,BMT中,4、8、12月龄的5×FAD 小鼠正确洞探洞次数不同程度减少(P<0.05,P<0.01),正确象限停留时间不同程度降低(P<0.01)。NOR实验中, 4、8、12月龄的5×FAD小鼠的认知系数不同程度降低(P<0.05)。OFT中,4、8、12月龄5×FAD小鼠的活动总距离、 中央区停留时间、直立探索次数不同程度减少(P<0.01)。EMP实验中,4、8、12月龄的5×FAD小鼠的开臂停留时 间及开臂向下探究次数不同程度减少(P<0.01),闭臂停留不同程度时间增加(P<0.01)。TST和FST中,4、8、12月 龄的5×FAD小鼠的不动时间不同程度增加(P<0.01)。SPT中,4、8、12月龄的5×FAD小鼠的蔗糖偏嗜度不同程度 降低(P<0.01)。涤痰汤可显著改善4月龄5×FAD小鼠的上述指标,对8、12月龄5×FAD小鼠的部分指标有所改 善。结论　涤痰汤可有效改善4月龄雄性5×FAD小鼠的焦虑抑郁状态,为临床应用提供了理论依据。

关键词: 阿尔茨海默病, β-淀粉样蛋白, 焦虑, 抑郁, 涤痰汤