目的探讨辛伐他汀对Aβ1-40诱导阿尔茨海默病(AD)大鼠模型学习记忆能力、海马β-分泌酶活性及Aβ表达的影响。方法选用健康雄性Wistar大鼠32只,随机分为4组,对照组、模型组、低、高剂量辛伐他汀组。除对照组双侧海马CA1区注射1μl生理盐水外,其余各组给予等容积聚集态Aβ1-40建立AD模型,并且各组按规定剂量灌胃4周。采用Morris水迷宫测试各组大鼠学习记忆能力;ELISA法测定海马组织匀浆中β-分泌酶的活性;免疫组化法观察各组海马Aβ的表达。结果低、高剂量辛伐他汀组能改善AD大鼠学习记忆能力(P<0.01),降低β-分泌酶活性(P<0.01),减少海马Aβ的表达(P<0.01),而低、高剂量辛伐他汀组二者相比无明显差异。结论辛伐他汀可改善AD大鼠模型学习记忆能力,可能与降低β-分泌酶活性、减少Aβ生成有关。 Objective To investigate the effects of simvastatin on learning and memory ability, β-secretase activity and Aβ expression in hippocampus of Aβ1-40-induced Alzheimer’s disease (AD) rats. Methods Thirty-two healthy male Wistar rats were randomly divided into 4 groups: control group, model group, low and high dose simvastatin group. Except for 1μl saline injected into CA1 area of ​​bilateral hippocampus in control group, the other groups were given the same volume of aggregated Aβ1-40 to establish AD model, and each group were given gavage for 4 weeks at the prescribed dose. Morris water maze was used to test the learning and memory abilities of rats in each group. The activity of β-secretase in hippocampus homogenate was measured by ELISA. The expression of Aβ in hippocampus was observed by immunohistochemistry. Results Low and high doses of simvastatin could improve the learning and memory ability of AD rats (P <0.01), decrease the activity of β-secretase (P <0.01) and decrease the expression of Aβ in hippocampus (P <0.01) There was no significant difference between the two groups in the dose of simvastatin. Conclusion Simvastatin can improve the learning and memory abilities of AD rats, which may be related to the decrease of β-secretase activity and the decrease of Aβ production.