【摘要】 目的探讨大豆异黄酮(SIF)单独或联合叶酸(FA)拮抗β淀粉样肽(Aβ)致大鼠学习记忆损伤的神经保护作用及其机制。方法(1)神经毒性研究Wistar大鼠随机分为4组,每组15只,分别于侧脑室注射生理盐水、Aβ25-35、Aβ31-35和Aβ1-40。于术后7d,Morris水迷宫试验检测大鼠学习记忆能力;术后14d,免疫组织化学法检测大脑Aβ阳性表达细胞数及脑组织中抗氧化相关指标,观察不同Aβ片段的神经毒性。(2)干预研究实验分为5组(对照、Aβ模型、SIF、FA、SIF与SIF+FA干预组),每组15只,分别灌胃0.5%羧甲基纤维素钠(CMC-Na)、0.5%的CMC-Na、SIF(160mg/kg bw·d)、FA(0.7mg/kg bw·d)和SIF(160mg/kg bw·d)+FA(0.7mg/kg bw·d),14d后,对照组于侧脑室注射生理盐水,Aβ模型、SIF、FA、SIF+FA干预组于侧脑室注射Aβ1-40,检测指标同毒性实验。结果(1)与对照组相比,Aβ25-35、Aβ1-40组大鼠平均逃避潜伏期和总路程显著延长;Aβ25-35、Aβ31-35和Aβ1-40组大鼠大脑皮质Aβ阳性表达细胞数显著增加,Aβ31-35和Aβ1-40组大鼠海马CA1区Aβ阳性表达细胞数显著增加;脑组织中AOC、GSH水平显著降低。(2)与模型组相比,SIF、FA和SIF+FA干预组大鼠平均逃避潜伏期显著缩短;大脑皮质和海马CA1区Aβ阳性表达细胞数显著减少;脑组织中AOC和GSH水平显著增高。结论三种Aβ片段均可引起大鼠学习能力障碍,其作用机制可能与Aβ介导的神经氧化损伤和脑内Aβ沉积直接神经毒作用有关;单独SIF或FA以及二者联合均可拮抗Aβ介导的大鼠神经毒性,发挥神经保护作用。更多还原

【Abstract】 Objective To study the β-amyloid peptide(Aβ) induced neurotoxicity and investigate the neuroprotective effects of SIF alone or SIF combined with FA. Method(1) The neurotoxicity study Sixty Wistar rats were randomly divided into control,Aβ25-35,Aβ31-35 and Aβ1-40 group,of 15 rats each. The ability of learning and memory was measured by Morris water maze at D8 after Aβ injection. The activity of AOC,GSH,and GSH-Px and levels of MDA in brain were measured,and the pathological changes in cerebral cortex and hippocampus CA1 of rats were measured by immunohistochemical method at D15 after Aβ injection.(2) The neuroprotective study:Seventy five rats were randomly divided into control,Aβ,SIF,FA and SIF+FA group,of 15 rats each. The rats in SIF,FA and SIF+FA group were treated i.g. by SIF and/or FA daily14 days before Aβinjection. Results(1) Compared with the control group,the mean escape latency and total distance in Aβ25-35 and Aβ1-40 group were significantly prolonged in Morris water maze test. The amounts of Aβ positive cells in cerebral cortex in Aβ25-35,Aβ31-35 and Aβ1-40 group were significantly increased,and the amounts of Aβ positive cells in hippocampus CA1 in Aβ31-35 and Aβ1-40 group were significantly increased. The levels of AOC and GSH in brain in Aβ25-35,Aβ31-35 and Aβ1-40 group were significantly decreased.(2) Compared with Aβ group,the mean escape latency in SIF,FA,SIF+FA group were significantly shortened,the amounts of Aβ positive cells were significantly decreased in cerebral cortex and hippocampus CA1,while the levels of AOC and GSH were significantly increased in brain.Conclusion Learning and memory impairment of rats could be induced by Aβ25-35,Aβ31-35 and Aβ1-40,which was possibly related to the oxidative damage and the deposition of Aβ in brain. SIF and/or FA showed neuroprotective effects in rats impaired by Aβ.更多还原