中文摘要：

目的探讨慢性高同型半胱氨酸血症对老年大鼠学习记忆功能的影响及其机制。方法选取18月龄健康大鼠,尾静脉注射同型半胱氨酸（homocysteine,Hcy）生理盐水溶液制造高同型半胱氨酸血症模型组（Hcy）,给予叶酸和维生素B12（FB）作为治疗组,持续6个月。Morris水迷宫检测大鼠学习和记忆能力;Western blot检测记忆相关分子的变化。结果①成功构建高同型半胱氨酸血症大鼠模型,尾静脉注射同型半胱氨酸后血浆同型半胱氨酸平均水平由对照组（8.6±1.1）μmol/L增高到（15.2±1.2）μmol/L,同时补充FB后血浆同型半胱氨酸平均水平下降到（12.6±1.1）μmol/L;②高同型半胱氨酸血症导致大鼠记忆障碍,补充FB能够有效改善记忆能力,对学习能力没有影响;③高同型半胱氨酸血症可使蛋白激酶A（PKA）催化亚基（PKA-Cα）和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）的水平明显下降,而补充FB可明显提高PKA-Cα和p-CREB的水平。结论补充FB能够有效改善高同型半胱氨酸血症所诱导的阿尔茨海默样记忆障碍,其机制可能与PKA及CREB有关。

英文摘要：

Objective To explore the effect of chronic hyperhomocysteinemia on Alzheimer-like pathologies and the underlying mechanisms in aged rats.Methods The hyperhomocysteinemia model was made by injection of homocysteine（Hcy）into the tail vein in 18-month old healthy rats（model group）,and folate and vitamin B12（FB）were given for 6 months as treatment group.The Morris water maze was used to test the learning and memory abilities,and Western blotting was used to detect the changes in PKA and CREB.Results ①Hcy levels were significantly increased from（8.6±1.1） to（15.2±1.2） μmol/L after injection of Hcy,and they decreased to（12.6±1.1） μmol/L after supplementation of FB;②Hyperhomocysteinemia led to the memory impairment of the aged rat,which was ameliorated by supplementation of FB,but FB had no effect on the learning abilities of the rats;③Hyperhomocysteinemia inactivated PKA and CREB,and supplementation of FB could increase the activities of PKA and CREB.Conclusion Supplementation of FB can ameliorate the hyperhomocysteinemia-induced Alzheimer-like memory impairment possibly through regulating the PKA and p-CREB in aged rats.