论文部分内容阅读
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 amyloid-beta 1-42 (Aβ1-42) -mediated spatial learning and memory impairment in rats and its mechanism of action. Methods Three-month-old male Wistar rats were randomly divided into five groups according to body weight: control group, Aβ model group, SIF low dose group, SIF middle dose group and SIF high dose group. Each dose of SIF was administered daily 40, 80 and 160 mg / kg body weight. The rats in the control group and model group were orally administered with the same amount of 0.5% CMC-Na. After continuous intragastric administration for 14 days, Aβ1-42 was injected into bilateral hippocampal CA1 area of model and experimental groups, Preparation of rat learning and memory impairment model. The control group was injected with the same amount of normal saline, and Morris water maze was used to detect learning and memory abilities on the 7th day after operation. On the 14th day after operation, femoral arteries were sacrificed and decapitated. Antioxidant indexes such as serum AOC, MDA, GSH-Px, Mineral elements Calcium, magnesium, manganese, iron, zinc and copper levels. Compared with the Aβ model group, the latency and total distance of the SIF groups were significantly shorter than that of the Aβ group (P <0.05). The latency of the SIF high-dose group was significantly shorter than that of the low-dose group (P <0.05) ; 2. Compared with Aβ model group, serum AOC level and GSH-Px activity in SIF groups were significantly increased and MDA levels were significantly decreased (P <0.05); serum AOC levels in SIF and high-dose groups were higher than those in low- (P <0.05) .3. Compared with the Aβ model group, the differences of the content of zinc and copper / zinc in SIF low, medium and high dose groups were statistically significant (P <0.05). The contents of copper in SIF medium and high dose groups were significantly decreased (P <0.05), and the copper content and copper / zinc value in SIF high dose group were lower than those in low dose group. Conclusions SIF can effectively improve the spatial learning and memory abilities of rats. It may be through improving the body’s redox status, raising the level of antioxidation, regulating the balance of mineral elements in brain, and then antagonizing the Aβ-mediated neurotoxicity and exerting its neuroprotective effects. And in a certain range showed dose-response relationship.