中文摘要：

目的探讨nAChR激动剂尼古丁对β-淀粉样蛋白（Aβ25-35）诱导的学习记忆障碍小鼠模型的治疗作用以及可能的作用机制。方法小鼠侧脑室注入凝聚态Aβ25-354.5。次日，用药组给予尼古丁0．2和2mg·kg-1（ip，bid×7d），对照组及模型组ip生理盐水。给药结束4d后（造模成功后11d），进行各组行为学及皮层、海马组织乙酰胆碱酯酶（AChE）、胆碱乙酰转移酶（ChAT）、丙二醛（MDA）、谷胱甘肽（GSH）活性指标的检测。结果定位航行实验发现，训练d4，模型组小鼠的上台潜伏期和游泳距离明显高于对照组和0．2、2mg·kg-1尼古丁治疗组（P〈0．01）；空间搜索实验发现，实验d5撤除平台，模型组在平台所在象限（第Ⅱ象限）中游泳的时间百分比明显低于对照组（P〈0．01）和0．2及2mg·kg-1尼古丁治疗组（P〈0．05）；模型组在平台所在象限（第Ⅱ象限）中游泳的距离百分比明显低于对照组（P〈0．01），但与0．2及2mg·kg-1尼古丁治疗组无差别（P〉0．05）。酶活性检测发现尼古丁治疗组的AChE及ChAT的活性较对照组明显升高（P〈0．01）；尼古丁治疗组（2mg·kg-1）MDA的活性较模型组明显降低（P〈0．01），尼古丁治疗组（0．2mg·kg-1）的活性较模型组无改变（P〉0．05）；尼古丁治疗组的GSH活性较模型组明显升高（P〈0．01）。结论尼古丁能够改善Aβ25-35诱导痴呆小鼠的学习记忆功能障碍，该作用与其增强ChAT的活性以及抗氧化应激有关。

英文摘要：

Aim To investigate the effects of nAChR agonist -nicontine in a mice model of Alzheimer＇s dis- ease（AD） rendered by Aβ25-35. Methods Mice were administered nicotine （0. 2,2 mg · kg - 1 ip, bid） for 7 d and control mice received daily ip injections of saline after the intracerebroventricular injection of aggregated Aβ25-35. After the last treatment, passive avoidance and performance in the Morris water maze （MWM） were assessed. The activities of cortical and hippocam- pal CHAT, ACHE, MDA and GSH were detected after the final behavioral test. Results Nicotine （ 0. 2, 2 mg·kg -1 ip, bid） significantly ameliorated the learn- ing and memory impairment induced by Aβ25-35. Nicotine （0. 2,2 mg · kg-1） decreased the latencies and swim distances of mice to reach a hidden platform and improved the corresponding changes in search strate- gies occurred in the Morris water maze. Biochemical a- nalysis showed that Nicotine （0. 2,2 mg· kg-1） pre- vented the decline of cortical and hippocampal ChAT and GSH activities induced by Aβ25-35, and showed in- hibition of the activity of MDA, although Aβ25-35 showed no effect on the cortical and hippocampal AChE activity compared with the Aβ25-35-induced mice groups. Conclusion Nicotine can reverse Aβ25-35-in- duced memory retrieval deficits in mice, and this effect was mediated by enhanced activity of ChAT and the inhibition of oxidative stress.