摘要
目的研究不同剂量大豆异黄酮(SIF)对β淀粉样肽1-42(Aβ1-42)介导的空间学习记忆损伤大鼠的神经保护作用,并探讨其作用机制。方法按体重将3月龄雄性Wistar大鼠随机分为5组:对照组、Aβ模型组、SIF低剂量组、SIF中剂量组、SIF高剂量组每组12只,SIF灌胃剂量分别为每天每公斤体重40、80和160 mg,对照组和模型组灌胃等量的0.5%CMC-Na,连续灌胃14 d后,模型组和实验组大鼠双侧海马CA1区注射Aβ1-42,制备大鼠学习记忆损伤模型。对照组注射等量生理盐水,于术后7 d,Morris水迷宫检测学习记忆能力;术后14 d,股动脉采血,断头处死,测定血清AOC、MDA、GSH-Px等抗氧化指标和脑矿物元素钙、镁、锰、铁、锌和铜的水平。结果1.与Aβ模型组比,SIF各剂量组潜伏期和总路程明显缩短,在平台象限距离的百分比明显增高(P<0.05),SIF高剂量组潜伏期比低剂量组缩短明显(P<0.05);2.与Aβ模型组比,SIF各剂量组血清AOC水平和GSH-Px活力显著增高,MDA水平显著降低(P<0.05),SIF中和高剂量组血清AOC水平高于低剂量组,SIF高剂量组MDA水平低于低剂量组,差异均有统计学意义(P<0.05);3.与Aβ模型组比,SIF低、中、高剂量组锌含量和铜/锌值差异均有统计学意义(P<0.05),SIF中、高剂量组铜含量显著减少(P<0.05),并且SIF高剂量组铜含量和铜/锌值低于低剂量组。结论SIF可有效改善大鼠的空间学习记忆能力,可能是通过改善机体氧化还原状态,提高抗氧化水平,调节脑内矿物元素的平衡,进而拮抗Aβ介导的神经毒性,发挥其神经保护作用,并且在一定范围内表现出剂量-反应关系。
Objective To study the neuroprotective effects of different doses of soybean isoflavone（SIF） on the spatial learning and memory ability impairment induced by beta amyloid 1-42 as well as the possible mechanism in rats.Method According to body weight,all experimental rats（male,aged 3 months） were randomly divided into control,Aβ treatment,and low,middle and high dose SIF groups,respectively,and each group including 12 rats.The rats in SIF low,middle and high dose groups were treated by i.g.40,80 or 160 mg/kg·BW·d SIF daily for 14 days before Aβ injection,while the rats in control group and Aβ group were treated by 0.5% CMC-Na.Morris Water Maze measured the abilities of rat learning and memory on the 7th day after Aβ injection.On the 14th day after Aβ injection,the rats were killed and blood were sampled and centrifuged to obtain serum.The levels or activity of AOC,MDA,GSH-Px in serum and the contents of Ca,Mg,Mn,Fe,Zn and Cu in brain tissue were determined.Results 1.Comparing with the Aβ treatment group,the mean escape latencies and total distances of rats in low,middle and high dose SIF groups were significantly shortened（P〈0.05）,the percentage of swimming in the quadrant with the platform was significantly increased（P〈0.05）.The mean escape latency of rats in high dose SIF group was significantly shortened than that of low dose SIF group（P〈0.05）.2.Comparing with the Aβ treatment group,the serum AOC level and GSH-Px activity in SIF low,middle and high dose groups were significantly increased（P〈0.05）,and the level of serum MDA was significantly decreased（P〈0.05）.The serum AOC levels both in middle and high dose SIF groups were much higher than the AOC level in low dose SIF group（P〈0.05）.The serum MDA level in high dose SIF group was much lower than the MDA level in low dose SIF group（P〈0.05）.3.Comparing with Aβ treatment group,the contents of Zn and Cu/Zn ratio in brain tissue in low,middle and high dose SIF groups were significantly different（P〈0.05）.The contents of Cu in middle and high dose SIF groups were much lower（P〈0.05）.The contents of Cu and Cu/Zn ratio in high dose SIF group were lower than that in low dose SIF group（P〈0.05）.Conclusion SIF could improve the spatial learning and memory ability in Aβ-induced neuro damage rats.The ability of changing the redox state,increasing the antioxidative level and balancing the mineral ratio in brain are the possible mechanisms that SIF exhibited neuro-protective effects in rats.
出处
《中国食品卫生杂志》
北大核心
2009年第1期4-8,共5页
Chinese Journal of Food Hygiene
基金
国家自然科学基金(30571560
30771802)
北京市教育委员会科技发展计划资助项目(KM200610025010
KZ200710025011)
