褪黑素对痴呆大鼠胆碱能功能的修复

Improvement of the cholinergic function by melatonin in amnesic rats induced by amyloid β-peptide 25～35

目的 通过观察褪黑素对淀粉样 β多肽 2 5～ 35片段(Aβ2 5～ 3 5)所致学习记忆功能障碍大鼠海马胆碱乙酰转移酶(ChAT)和胆碱酯酶 (AChE)活性的影响 ,从而探讨Aβ和胆碱能系统在阿尔采末病 (AD)病理机制中的作用 ,以期为AD的有效治疗提供新的思路。方法 采用双侧海马内注射Aβ2 5～ 3 5诱导大鼠学习记忆功能障碍模型 ;用Moriss水迷宫法检测学习记忆功能 ;分别使用免疫组化和比色法检测ChAT和AChE的变化。结果 大鼠双侧海马内注射Aβ2 5～ 3 5(2 0 μg)可引起大鼠空间学习记忆功能障碍 ,ChAT免疫反应阳性神经元数量减少 ,且着色变淡 ;而脑组织中胆碱酯酶的活性改变不显著。褪黑素 (0 1、1、10mg·kg-1)连续给予 (ig) 10d ,对上述改变有不同程度的拮抗作用。 结论 褪黑素改善Aβ2 5～ 3

AIM To investigate whether melatonin improve the learning and memory dysfunction in the amnesic rats induced by amyloid β peptide 25～35 (Aβ 25～35 ) via cholinergic nervous system or not.Methods The amnesic model in adult rats was induced by injection of Aβ 25～35 into hippocampus; Morris water maze was used to determine the effects of Aβ 25～35 and melatonin on the learning and memory. The activity of the choline acetyltransferase and acetylcholinesterase were determined by immunohistochemistry and spectrophotometry respectively. RESULTS Injection of Aβ 25～35 20 μginto the adult rats hippocampus induced learning and memory dysfunction, and a decrease in the number of ChAT immunoreactive neurons in hippocampus. Melatonin (0 1, 1, and 10 mg·kg -1 , ig×10 d) improved the Aβ 25～35 treated rats cognitive function and increased the number of ChAT immunoreactive neurons in hippocampus. CONCLUSION Improvement of the cholinergic dysfunction by melatonin in adult rats induced by amyloid β peptide 25～35 may be via cholinergic nervous system.