新药T-006对东莨菪碱所致记忆障碍模型动物学习记忆的改善作用  

Effects of new drug T-006 on improving learning and memory abilities in scopolamine-induced dementia Kunming mice

作　　者：宋奇[1] 王琴[1] 吴韦黎[1] 邵敏[1] 张宇[1] 张在军[2] 王玉强[2] 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 [2]暨南大学药学院新药研究所,广东广州510632

出　　处：《中国药理学通报》2016年第6期812-817,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金项目(No 81373439);广东省科技计划项目(No 2014A020209032);广州市科技局科技攻关引导项目(No 201300000158)

摘　　要：目的探讨新药T-006对东莨菪碱所致小鼠学习记忆障碍的影响及其作用机制。方法将72只♂昆明小鼠随机分为6组:正常对照组、模型组(给予东莨菪碱)、阳性药对照组(多奈哌齐+东莨菪碱)、T-006组(T-006+东莨菪碱,包括T-006 1 mg·kg^(-1)组、T-006 3 mg·kg^(-1)组和T-006 10 mg·kg^(-1)组)。连续给药14 d,给药d 11进行Morris水迷宫实验。水迷宫实验连续进行5 d,前4 d为定位航行实验,d 5为空间探索实验。定位航行实验时,除正常对照组外,每天每只小鼠于入水前20 min腹腔注射2 mg·kg^(-1)东莨菪碱造模,正常对照组腹腔注射等量无菌生理盐水。空间探索实验时,实验动物不再给予东莨菪碱造模并且不进行T-006给药。5 d水迷宫实验结束后,立即取样并检测大脑海马和皮层抗氧化能力相关指标以及乙酰胆碱酯酶活性。结果与正常对照组比较,模型组小鼠学习记忆能力明显降低,海马和皮层中超氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)含量明显下降,丙二醛(MDA)含量明显升高,乙酰胆碱酯酶(Ach E)活性明显增高;各剂量的T-006均能明显改善小鼠学习记忆障碍,所试剂量(3、10 mg·kg^(-1))的T-006明显提高脑组织中SOD活性和GSH含量,并降低MDA含量和ACh E活性。结论 T-006能明显改善东莨菪碱所致小鼠学习记忆障碍,该作用机制可能与其抗氧化作用以及抑制乙酰胆碱酯酶活性有关。Aim To explore the effects of new drug T- 006 on improving learning and memory abilities in scopolamine-induced dementia mice and its possible mechanism. Methods 72 male Kunming mice were randomly divided into six groups: normal control group,model group,donepezil treatment group,T-006 treatment group with different doses( 1,3 and 10mg·kg^(-1)). All mice were treated by intragastric administration for 14 consecutive days. Learning and memory abilities were tested by a five-day Morris water maze trial from the 11 th day. the first 4 days of the five-day Morris water maze,the navigation test was performed,the last day of Morris water maze is the spatial probe test. During the navigation test, mice were intraperitoneally given 2 mg · kg^(-1)scopolamine20 minutes before entering the water,while normal control group mice administrated with sterile saline instead. Mice were not given T- 006 nor scopolamine in spatial probe test. After Morris water maze,all mice were sacrificed for hippocampus and cortex. The activities of Ach E and SOD and the levels of GSH and MDA in hippocampus and cortex were measured after tissue harvesting. Results Compared with model group,T-006 could obviously improve learning and memory abilities in scopolamine-induced mice, significantly increase the levels of SOD and GSH and decrease the levels of MDA and Ach E. Conclusion T- 006 can significantly improve cognitive abilities in scopolamineinduced dementia mice,and its relevant mechanism may be closely related to its antioxidative effect and the ability to decrease Ach E level.

关 键 词：T-006 东莨菪碱 MORRIS水迷宫 昆明小鼠 海马 皮层 学习记忆能力 

分 类 号：R-332[医药卫生] R322.81