【摘要】 目的观察α-玉米赤霉醇(α-ZAL)对阿尔茨海默病(AD)小鼠模型认知行为的改善作用及其机制。方法将40只成年雌性小鼠随机分为对照组、模型组、苯甲酸雌二醇(EB)组和α-ZAL组,每组10只。除对照组外,其他组于实验开始后第7天于脑室内注射β-淀粉样蛋白(Aβ25-35)3 nmol造成拟AD痴呆模型。对照组和模型组肌肉注射橄榄油0.05 ml/d,共14 d;EB组肌肉注射EB0.1 nmol/d,共14 d;α-ZAL组肌肉注射α-ZAL 0.1nmol/d,共14 d。Morris水迷宫检测小鼠空间学习记忆能力。分光光度法和同位素法测脑内氧化应激指标和一氧化氮(NO)系统改变。结果模型组Morris水迷宫末次寻台潜伏期明显延长(P<0.01),EB组和α-ZAL组较模型组缩短(P<0.05)。模型组脑内过氧化物歧化酶(SOD)、谷胱甘肽过氧物酶(GSH-Px)下降(P<0.05),丙二醛(MDA)、原生型一氧化氮合酶(cNOS)、诱生型一氧化氮合酶(iNOS)和NO上升(P<0.05);除α-ZAL组海马SOD和cNOS外(P>0.05),EB组和α-ZAL组各指标均优于模型组(P<0.01)。EB组和α-ZAL组之间无显著性差异(P>0.05)。结论α-ZAL和EB一样能通过提高脑内抗氧化和降低脂质过氧化能力,拮抗Aβ和NO的神经毒性,明显改善AD模型小鼠的认知行为。更多还原

【Abstract】 Objective To explore the effect of α-zearalanol(α-ZAL) on β-amyloid(Aβ) induced mice and the mechanism. Methods The model was induced by intracerebroventricular injection of Aβ25-35. The mice were divided randomly into sham group, model group, estradiol benzoate(EB) group(Aβ+EB) as a positive control and α-ZAL(Aβ+α-ZAL) group. Morris water maze was used to evaluate the learning and memory ability. The levels of antioxidant enzymes and nitric oxide system in the brain tissue were detected with spectrophotometric and sotopic method. Results The escape latency was longer in the model group than in the control group(P<0.01), and was shorter in the EB group and α-ZAL group than in the model group(P<0.05). Compared with the control group, the level of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) decreased, and the level of malonaldehyde(MDA), constitutive nitric oxide synthase(cNOS), inducible nitrous oxide synthesis(iNOS), and nitric oxide(NO) increased in the model group(P<0.05); compared with the model group, the level of SOD and GSH-Px increased, and the level of MDA, cNOS, iNOS and NO decreased in the EB group and α-ZAL group(P<0.05), except the level of SOD and cNOS in hippocampus in α-ZAL group(P>0.05). There was no significant difference between EB group and α-ZAL group(P>0.05). Conclusion α-ZAL could improve the cognitive behavior in Aβ25- 35 induced mice by increasing the antioxidant activities and decreasing the lipid peroxidation.更多还原