一氧化氮和天然抗氧化剂对阿尔茨海默症的潜在防治作用

Preventive and Therapeutic Effects of Nitric Oxide and Natural Antioxidants on Alzheimer’s Disease

摘要: 本文以转基因细胞和线虫体系为模型，研究了一氧化氮(nitric oxide, NO)和天然抗氧化剂的合理搭配组合对阿尔茨海默症(Alzheimer’s disease, AD)的防治作用。结果发现，低浓度的NO可以通过降低细胞内活性氧的水平保护神经细胞，防止APPsw和ApoE4过量表达引起的损伤作用；而高浓度的NO可以通过增强活性氧(reactive oxygen species, ROS)的产生加剧神经细胞损伤。适量NO和天然抗氧化剂都对Abeta转基因诱导的线虫瘫痪行为具有抑制作用。NO和天然抗氧化剂的合理搭配组合既可以通过显著清除ROS抑制ApoE4和APPsw转基因引起的细胞活力降低，又可以更好的延缓Abeta转基因诱导的线虫瘫痪行为。这些结果说明，NO和天然抗氧化剂合理搭配可以在AD细胞和线虫模型中抑制转基因引起的细胞和线虫的损伤，有可能对AD具有一定的防治作用。

Abstract: In this study, the preventive and therapeutic potential of nitric oxide (NO) and natural antioxidants on Alzheimer’s disease (AD) were studied using transgenic cells and C. elegans models. It was found that low concentration of NO protected neuronal cells by reducing the production of reactive oxygen species (ROS). In contrast, high concentration of NO aggravated the cell damage by producing more ROS. Low concentration of NO and natural antioxidant could protect C. elegans against paralysis induced by expression of transgenic Abeta gene. It was found that a formulation of L-arginine and natural antioxidants increased the viability of N2a cells overexpressing APPsw and ApoE4 by scavenging ROS. This formula also protected C. elegans against paralysis caused by transgenic Abeta gene. These results suggest that this formulation of NO precursor and natural antioxidants may have a potential for prevention and treatment of AD.