益智胶囊对阿尔茨海默病大鼠学习记忆能力的改善作用

Effects of Yizhi Capsule on Learning and Memory in Rat AD Model

摘要:

目的: 探讨益智胶囊对海马注射β淀粉样蛋白(1-42)(Aβ_1-42)引起阿尔茨海默病(AD)大鼠学习记忆能力和胆碱能系统以及Tau蛋白磷酸化水平的影响。方法: 将SD大鼠随机分为正常组、假手术组、模型组、阳性药石杉碱甲组、益智胶囊(低、中、高)3个剂量组,假手术组右侧海马单次注射生理盐水5 μL,模型组、阳性药组及益智胶囊各组分别右侧海马单次注射Aβ_1-42(2 g·L^-1)5 μL, 益智胶囊组和阳性药组用益智胶囊提取物(1.78,3.56,7.12 g·kg^-1)和石杉碱甲(60 μg·kg^-1)连续灌胃给药31 d,1次/d,其余3组同样方法给予生理盐水。给药21 d后,以Morris水迷宫实验测试各组大鼠学习记忆能力,连续10 d,训练期间继续给药;水迷宫实验结束后,生化检测胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AchE)的活性;Western blot法定量检测海马神经元Aβ蛋白表达变及Tau蛋白(Ser262)的磷酸化程度。结果: 与正常对照组相比,假手术组的游泳总路程和逃避潜伏期未见明显统计学差异;与假手术组相比,模型组的游泳总路程和逃避潜伏期均明显延长,且均具有统计学差异;与模型组相比,其他各组AD大鼠的游泳总路程和逃避潜伏期均明显缩短,空间探索试验给药组穿越站台的次数明显增加;与模型组相比,给药组 AchE活性降低,ChAT活性升高;Aβ蛋白的表达和Tau(S262)磷酸化水平均降低。结论: 益智胶囊能改善Aβ_1-42引起的AD大鼠学习记忆障碍,其作用机制可能是增加中枢胆碱能系统Ach的含量和抑制Tau蛋白过度磷酸化。

Abstract:

Objective: To observe the effects and mechanisms of Yizhi capsule on beta-amyloid protein 1-42 (Aβ_1-42)induced learning memory disorders and cholinergic system in rat Alzheimer's disease(AD) model. Method: The SD rats were randomly divided into seven groups, single dose normal saline(NS, 5 μL) was given via right hippocampus injection to sham group, single dose Aβ_1-42(2 g·L^-1) 5 μL was given via right hippocampus injection to model group and the treatment groups were orally given Yizhi capsules for one month. After 21 days of administration, Morris water maze was used to measure learning and memory performance.The rats of treatment groups were given Yizhi caspase for 10 days. After the watermaze experiment, biochemical detection choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) activity were measured.The protein expressions of Aβ,P-tau(S262) were determined by Western blot method. Result: Compared with normal group, and in the total distance and escape latency sham group had no difference. Compared with sham group, in model group the total distance and escape latency were significantly prolonged, and differences was statistically significant(P<0.01). Compared with model group,in other groups the total distance and escape latency were significantly shorten(P<0.05,P<0.01), the AchE of enzymeactivity was significantly lower and increased ChAT enzyme activity,the phosphorylation of Aβ_1-42and Tau at Ser262 were decreased in other groups. Conclusion: Yizhi capsule can attenuate the learning and memory impairment induced by Aβ_1-42, which maybe related to increasing the cholinergic system of the central nervous system and suppressing Tau protein.