淫羊藿苷对淀粉样β蛋白片段25-35所致大鼠学习记忆障碍的改善作用

目的观察淫羊藿苷对淀粉样β蛋白片段25-35(Aβ25-35)所致阿尔茨海默病(AD)模型大鼠学习记忆能力的保护作用,并探讨其可能的作用机制。方法Wistar雄性大鼠,右侧海马内注射Aβ25-3510μg制备AD模型,次日起淫羊藿苷30,60和120mg.kg-1灌胃给药,连续14d,d15～19Morris水迷宫检测大鼠空间辨别学习记忆能力;d20检测海马组织中谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)及一氧化氮合酶(NOS)的活性,免疫组化法检测海马内乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的表达。结果与模型对照组比较,淫羊藿苷给药14d明显改善大鼠学习记忆能力;海马组织中SOD和GSH-PX活性升高,NOS活性降低;海马内AChE及ChAT的表达增加。结论淫羊藿苷可以改善Aβ25-35海马内注射所致AD模型大鼠的学习记忆能力,其作用可能与其增加AChE和ChAT表达,增强SOD和GSH-PX等自由基清除酶活性,降低NOS活性,减少NO释放等多种机制,促进胆碱能递质系统功能的恢复有关。

Protective effects of icariin on learning and memory dysfunction induced by amyloid β-protein fragment 25-35

AIM To investigate the protective effects of icariin on the learning and memory abilities in Alzheimer′s disease (AD) model rats, and explore its potential mechanisms. METHODS AD model was induced by hippocampus-injection with amyloid β-protein fragment 25-35 (Aβ_25-35) 10 μg. From the next day, icariin 30, 60 or 120 mg·kg^-1 was administered by gavage for 14 d. The abilities of spatial learning and memory were tested by Morris water maze from d 15 to d 19. The expressions of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) in hippocampus were detected by immunohistochemistry and quantitated analysis by BI2000 image analysis system. The activities of nitric oxide synthase (NOS), superoxide dismuase (SOD) and glutathione peroxidase (GSH-PX) in hippocampus were assayed by photochemical method in d 20. RESULTS Compared with AD model rats, icariin treatments significantly caused the decreases in escape latency and searching distance in the Morris water maze test, increased the expressions of AChE and ChAT, enhanced the activities of SOD and GSH-PX, and decreased the activity of NOS in hippocampus. CONCLUSION Icariin can improve the learning and memory abilities in Aβ_25-35 induced AD rats. The mechanisms may be related to its improving effect on the cholinergic transmitter metabolism of central nervous system, resulted from increment of AChE and ChAT expressions, anti-oxidative capability and inhibitory activity of NOS.