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目的:探讨益智胶囊对海马注射β淀粉样蛋白(1-42)(Aβ1-42)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5μL,模型组、阳性药组及益智胶囊各组分别右侧海马单次注射Aβ1-42(2 g·L-1)5μL,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(60μg·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(Ch AT)和乙酰胆碱酯酶(Ach E)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Ach E活性降低,Ch AT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Aβ1-42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。
Objective: To investigate the effects of Yizhi capsule on learning and memory abilities, phosphorylation of cholinergic system and Tau protein in Alzheimer’s disease (AD) -induced hippocampal injection of β-amyloid (1-42) (Aβ1-42) . Methods: SD rats were randomly divided into three groups: normal group, sham operation group, model group, huperzine A group and Yizhi capsule (low, medium and high) 5μL normal saline and 5μL Aβ1-42 (2 g · L-1) were injected into the right hippocampal of the model group, the positive medicine group and the Yizhi capsule respectively. The Yizhi capsule group and the positive medicine group were treated with the Yizhi capsule extract (1.78,3.56,7.12 g · kg-1) and huperzine A (60 μg · kg-1) were given intragastrically for 31 days once a day, and the other three groups were given the same way of saline. After 21 days of administration, the learning and memory abilities of rats in each group were tested by Morris water maze test for 10 consecutive days and continued during training. After the water maze test, biochemical detection of ChAT and acetylcholinesterase The activity of Ach E was detected by Western blot. The level of Aβ protein in hippocampal neurons and phosphorylation of Tau protein (Ser262) were detected by Western blot. Results: Compared with the normal control group, there was no significant difference between the sham-operated group and the sham-operated group in the total swimming distance and escape latency. Compared with the sham-operated group, the total swimming distance and escape latency of the model group were significantly prolonged Compared with the model group, the total swimming distance and escape latency of AD rats in other groups were significantly shortened, and the number of drug discovery groups crossing the platform in space exploration test significantly increased. Compared with the model group, the Ach E Activity decreased, ChAT activity increased; Aβ protein expression and Tau (S262) phosphorylation levels were reduced. Conclusion: Yizhi capsule can improve the learning and memory impairment induced by Aβ1-42 in AD rats. Its mechanism may be to increase the content of central cholinergic system Ach and inhibit the hyperphosphorylation of Tau protein.