六味地黄丸对APP/PS1小鼠学习记忆能力及胆碱能系统的影响

目的:探讨六味地黄丸对APP/PS1双转基因小鼠的学习记忆能力以及胆碱能系统的影响。方法:将40只APP/PS1双转基因小鼠随机分为APP/PS1模型组,六味地黄丸低、中、高剂量(0.59,1.18,2.36 g·kg^-1·d^-1)组,西药布洛芬(0.04 g·kg^-1·d^-1)组,每组8只。相匹配的3月龄野生型(WT)小鼠8只,作为正常组。ig给药3个月,通过Morris水迷宫检测学习记忆能力。采用酶联免疫吸附测定(ELISA)法检测各组小鼠大脑皮层乙酰胆碱(ACh)含量,乙酰胆碱转移酶(ChAT)和乙酰胆碱酯酶(AChE)的活性。结果:与正常组相比,APP/PS1模型组小鼠在各时期找到平台所需的时间(潜伏期)均延长(P<0.05),在平台所在象限停留时间,百分比,穿越平台次数均降低(P<0.05),ACh含量及ChAT活性均降低(P<0.05)。六味地黄丸低、中、高剂量组和布洛芬组与APP/PS1模型组相比潜伏期缩短(P<0.05),在平台所在象限停留时间,百分比,穿越平台次数均增高(P<0.05),ACh含量及ChAT活性均增高(P<0.05),AChE活性无统计学差异。结论:不同剂量的六味地黄丸可通过提高脑内ChAT活性,增加ACh含量影响中枢神经胆碱能系统,从而改善APP/PS1双转基因小鼠学习记忆能力。

Effects of Liuwei Dihuang Wan on Learning and Memory Abilities and Cholinergic System in APP/PS1 Mice

Objective: To investigate the effects of Liuwei Dihuang Wan on learning and memory abilities and activity of cholinergic system in APP/PS1 mice. Method: 40 double transgenic APP/PS1 mice were randomly divided into APP/PS1 model group, Liuwei Dihuang Wan low dose group (0.59 g·kg^-1·d^-1), medium dose group (1.18 g·kg^-1·d^-1), and high dose group (2.36 g·kg^-1·d^-1), ibuprofen group (0.04 g·kg^-1·d^-1), with 8 mice in each group. Another 8 3 month old wild type mice (WT) were selected as the normal group. After lavage administration for 3 months, Morris water maze was used to test their learning and memory abilities. The content of acetylcholine (ACh) and the activity of choline acetyltransferase (ChAT) and acetylcholinesterase(AChE) in cortex were measured by enzyme-linked immunosorbant assay(ELISA). Result: Compared with the normal control group, the time required to find the platform (latency) was longer in the model group of each period (P<0.05);time and percentage of staying in platform quadrant and frequency of crossing the platform were decreased (P<0.05);content of ACh and activity of ChAT were decreased (P<0.05). Compared with the APP/PS1 model group, latency was shortened (P<0.05), time and percentage of staying in platform quadrant and frequency of crossing the platform were increased (P<0.05) in Liuwei Dihuang Wan low, medium and high dose groups as well as ibuprofen group;the content of ACh and the activity of ChAT were increased (P<0.05), while the activity of AChE was not significantly different. Conclusion: Different doses of Liuwei Dihuang Wan can improve learning and memory abilities of APP/PS1 mice, which is related to its effects on the cholinergic system by increasing the content of ACh and the activity of ChAT.