新药AD-08对两种痴呆动物模型学习记忆障碍和海马乙酰胆碱酯酶活性的影响  

Effects of new drug AD-08 on spatial memory and acetylcholinesterase activity in two AD models

作　　者：左亮[1] 原冬冬[1] 张媛[1] 王琴[1] 陶亮[1] 

机构地区：[1]中山大学中山医学院药理学教研室,广东广州510080

出　　处：《中国药理学通报》2013年第9期1235-1238,共4页Chinese Pharmacological Bulletin

基　　金：新疆维吾尔自治区科技厅科技计划课题:"新疆创新药物临床前药效学评价技术平台建设"(No 201233150)

摘　　要：目的研究抗阿尔采末病（Alzheimer’Sdisease，AD）新药AD-08对动物学习记忆功能以及海马乙酰胆碱酯酶（AChE）活性的影响。方法采用侧脑室注射Aβ1-42蛋白的引起的痴呆大鼠模型和APP／PSl双转基因痴呆小鼠模型。SD大鼠分为正常组、模型组、多奈哌齐对照组、AD-08低、中、高剂量组。APP／PSl双转基因小鼠分为模型组、多奈哌齐对照组、AD-08低、中、高剂量组，以及用具有相同遗传背景的小鼠作为正常对照组。正常对照组及模型组动物每天固定时间灌胃给予相应剂量的药物溶剂（生理盐水）；阳性药对照组和AD-08各剂量组动物分别给予相应剂量的药物。SD大鼠给药8d，APP／PS1双转基因小鼠给药1个月，之后用Morris水迷宫方法对动物进行空间记忆能力测试。并用AChE活性试剂盒测定受试动物大脑海马组织的AChE活性。结果与正常对照组相比，痴呆模型组大鼠和小鼠的空间学习记忆能力均明显降低（P〈0．05），海马组织中的AChE活性明显升高（P〈0．05）。各剂量的AD-08均能够明显改善痴呆模型动物的空间学习记忆能力，并降低其海马组织AChE的活性（P〈0．05）。所试剂量（0．7mg·kg^-1 10mg·kg^-1）的AD-08改善痴呆模型动物空间学习记忆能力的作用与多奈哌齐（1mg·kg^-1～3mg·kg^-1相似（P〉0．05）。结论AD-08可以明显改善Aβ1-42所致的痴呆模型大鼠和APP／PS1双转基因痴呆模型小鼠的空间学习记忆能力；其作用机制可能与抑制海马AChE的活性有关。Aim To explore the effect of new drug AD- 08 on spatial memory and acetylcholinesterase activity of rats with Aβ1-42 induced Alzheimer Disease and APP/PS1 double-transgenie mice. Methods 48 SD male rats were randomly divided into six groups： con- trol group, AD group, Donepezil treatment group, AD- 08 treatment group with different doses. 8 rats in each group. Control group were established by injection of saline into lateral ventricle, and other groups injected with Aβ1-42 Both control group and AD group were treated with solvent by intragastric administration every morning; Donepezil treatment group and AD-08 treat- ment group were received Donepezil and AD-08 respec- tively. Spatial memory ability was tested with Morris water maze after 8 days of intragastric administration. APP/PS1 double-transgenic mice were also divided in- to six groups as SD rats model. Mice in control grouphad the same genetic background with APP/PS1 doub- le-transgenic mice. The intragastric administration was also the same as the SD rats model above. Morris water maze experiment was carried out one month later. After that, acetylcholinesterase activity of hippocampus was tested with Acetylcholinesterase Reagant kit. Results In both models of this experiment, spatial memory a- bility in AD group decreased obviously but acetylcho- linesterase activity of hippocampus increased compared with control group （ P 〈 0. 05 ） ; however, new drug AD-08 improved it just as Donepezil. Conclusion New drug AD-08 could improve spatial memory ability of the two kinds of models. It may be related with the acetylcholinesterase activity of hippocampus.

关 键 词：AD-08 多奈哌齐 淀粉样沉积蛋白 海马 阿尔采末病 乙酰胆碱酯酶 

分 类 号：R-332[医药卫生] R322.81