二苯乙烯苷对慢性脑缺血大鼠学习记忆的影响  

Effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside on learning and memory abilities of rats with chronic cerebral ischemia

作　　者：刘丽[1] 李林[1] 赵玲[1] 张丽[1] 李雅莉[1] 叶翠飞[1] 

机构地区：[1]首都医科大学宣武医院药物研究室教育部神经变性病学重点实验室

出　　处：《中国药理学与毒理学杂志》2008年第2期108-115,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点基础研究发展计划(2003CB517104);国家自然科学基金资助项目(90709011);国家自然科学基金资助项目(30500664);国家自然科学基金资助项目(30472184);北京市自然科学基金资助项目(7050001);北京市自然科学基金资助项目(7032013);北京市自然科学基金资助项目(7063079);首都医学发展基金资助项目(03Ⅲ21)~~

摘　　要：目的观察何首乌有效成分二苯乙烯苷(TSG)对慢性脑缺血大鼠学习记忆能力的影响,并探讨其可能机制。方法雄性SD大鼠双侧颈总动脉永久性结扎制备慢性脑缺血致痴呆模型。术前2周起,分别给TSG30,60及120mg·kg-1·d-1,ig,连续11周。术后8周时,分别用Morris水迷宫实验和避暗实验检测大鼠的空间学习记忆能力和被动回避学习记忆能力。术后9周时,采用生化方法检测海马乙酰胆碱酯酶(AChE)活性,免疫组化方法检测海马蛋白磷酸酶2A(PP-2A)和微管相关蛋白2(MAP-2)的表达。结果慢性脑缺血模型组大鼠空间和被动回避学习记忆能力明显降低,海马AChE活性显著升高,PP-2A和MAP-2表达明显减少。TSG给药10周可显著改善慢性脑缺血引起的学习记忆能力降低;给药11周明显抑制海马AChE活性增高,并增加PP-2A和MAP-2的表达。结论TSG可改善慢性脑缺血大鼠的学习记忆能力,其机制可能与抑制海马AChE活性,增加海马PP-2A和MAP-2的表达有关。AIM To detect the effect of 2,3,5,4＇-tetrahydroxystilbene-2-O- β-D-glucoside （TSG）, the main effective component of Polygonum multiflorum Thunb. , on learning and memory abilities of model rats with chronic cerebral ischemia and to discuss its possible mech-anisms. METHODS Models of chronic cerebral ischemia were induced by permanent ligation of bilateral carotid arteries in male SD rats. TSG （30, 60 and 120 mg.kg-1） was administrated ig, once daily for 11 weeks, from 2 weeks before the surgery to 9 weeks after the surgery. Morris water maze and step-through test were used to detect the space learning and memory abilities and the passive avoidance learning and memory abilities respectively at 8 weeks after the surgery. The biochemical method was used to determine the activity of acetylcholinesterase （AChE） in hippocampus and the immunohistochemistry method was applied in the examination of protein phosphatase-2A （PP-2A） and microtubule associated protein-2 （MAP-2） expression in hippocampus at 9 weeks after the surgery. RESULTS Both the space and passive avoidance learning and memory abilities were severely impaired in model rats compared with sham operation rats. The activity of AChE in hippocampus was significantly increased in model rats, while the expression of PP-2A and MAP-2 in hippocampal CA1 region was decreased. The 10-week ig administration of TSG markedly improved the learning and memory abilities of model rats, and the 11-week ig administration of TSG decreased the AChE activity and increased the ex-pression of PP-2A and MAP-2 in hippocampus. CONCLUSION TSG can improve the learning and memory abilities of chronic cerebral ischemic rats. The action of decreasing the AChE activity and increasing the expression of PP-2A and MAP-2 in hippocampus may be the potential mechanisms.

关 键 词：二苯乙烯苷 何首乌 脑缺血 学习 记忆 乙酰胆碱酯酶 磷蛋白磷酸酶 微管相关蛋白质类 

分 类 号：R749.16[医药卫生—神经病学与精神病学]