维生素E对D-半乳糖诱致衰老小鼠脑抗氧化能力、钙稳态和线粒体DNA(mtDNA)损伤的影响  

Influences of Vit-E on the mtDNA damage and Ca^(2+) homostasis of hippocampus and antioxidative ability in brain of aging mice induced by D-galactose

作　　者：曲娴[1] 方文娟[2] 李冰[1] 郑浩[1] 吕俊华[2] 

机构地区：[1]北华大学医学院,吉林吉林132013 [2]暨南大学药学院药理教研室,广东广州510632

出　　处：《中国病理生理杂志》2008年第3期523-526,共4页Chinese Journal of Pathophysiology

摘　　要：目的:探讨维生素E(Vit-E)对D-半乳糖诱致衰老小鼠脑抗氧化能力、胞浆游离Ca2+([Ca2+]i)稳态和线粒体DNA(mtDNA)损伤的影响。方法:小鼠连续皮下注射(sc)D-半乳糖(1 000 mg.k-1.d-1)8周制备衰老模型,并于第3周开始给予维生素E(100 mg.kg-1;250 mg.kg-1)处理;8周后采用水迷宫测定小鼠学习记忆能力,并取脑组织测定谷胱甘肽过氧化物酶(GSH-Px)和琥珀酸脱氢酶(SDH)活性,测定一氧化氮(NO)含量和一氧化氮合酶(NOS)活性。Fura-2/AM负载法和PCR方法分别测定海马神经细胞[Ca2+]i浓度和mtDNA缺失突变。结果:维生素E处理能明显改善D-半乳糖诱致衰老小鼠学习记忆障碍,抑制脑组织NOS活性,降低NO含量,提高GSH-Px和SDH活性,降低[Ca2+]i水平(P<0.01,P<0.05),并防止mtDNA缺失突变的发生。结论:维生素E具有提高衰老小鼠脑抗氧化能力和调节[Ca2+]i稳态的作用,并抑制氧化应激引起的mtD-NA损伤,从而改善衰老动物学习记忆障碍。AIM ： To study the influences of vitamin E （ Vit - E） on the mtDNA damage and Ca^2＋ homeostasis in hippocampus and antioxidative ability in aging brain induced by D - galactose. METHODS. D - galactose （ 1 000 mg·k^-1·d^-1 ） was injected into mice hypodermically for 8 weeks to induce aging animal model, and Vit - E （ 100 mg·kg^-1 ; 250 mg·kg^-1 ） was administered for 6 weeks by ig at the 3rd week of making model. After Vit - E treatment for 8 weeks, water maze test was used to determine the ability of mice＇ s learning and memory. The activities of glutathione peroxidase （GSH- Px） and succinate dehydrogenase （SDH）, the content of nitric oxide （NO） and activity of nitric oxide synthase （NOS） in the brain tissue were detected separately. Fura - 2/AM, double - wave - length fluorospectrophotometer and PCR method were used to measure the concentration of calcium ion and mtDNA mutation in the hippocampus cells. RESULTS ： Administration of Vit - E improved significantly the ability of learning and memory in model mice, inhibited the activity of NOS and decreased the amount of NO, and increased the activities of GSH - Px and SDH respectively in brain tissues, decreased the concentration of calcium ion （P 〈0. 01, P 〈0. 05）, and prevented the damage of mtDNA in hippocampus. CONCLUSION： Vit -E can enhance the antioxidative ability, regulate the homeostasis of Ca^2＋ and inhibit the damage of mtDNA caused by oxidative stress in aging brain, and improve the ability of learning and memory in aging mice.

关 键 词：半乳糖 衰老 线粒体 抗氧化剂 钙 维生素E 

分 类 号：R363[医药卫生—病理学]