PDF(Pubmed)
Abstract：
Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer\'s disease (AD), but the involvement of this stress at the peripheral level in the disease\'s onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer\'s disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.
摘要：
已知炎症-氧化应激在阿尔茨海默病(AD)的病理生物学中起着关键作用。但这种应激在外周水平与疾病发病的关系却鲜有研究。这项研究调查了来自AD（3xTgAD）和非转基因小鼠（NTg）的雌性三重转基因小鼠的腹膜白细胞中的促炎谱和氧化应激参数。在2、4、6、12和15月龄时获得腹膜白细胞。TNFα的浓度，INFγ,IL-1β,测量了在没有刺激的培养物中释放的IL-2，IL-6，IL-17和IL-10，并测量了丝裂原伴刀豆球蛋白A和脂多糖的存在。还原型谷胱甘肽（GSH）的浓度，氧化型谷胱甘肽(GSSG),脂质过氧化，和Hsp70也在腹膜细胞中进行了分析。我们的结果表明，尽管3xTgAD小鼠的促炎细胞因子释放较低，这种反应是不受控制和过度刺激的，尤其是在2个月大的前驱期。此外,在2个月和4个月时，3xTgAD的白细胞中GSH的浓度较低，脂质过氧化物的含量较高，还有,6个月时,较低浓度的Hsp70。总之,3xTgAD小鼠在前驱阶段表现出比NTg小鼠更差的促炎反应和更高的氧化应激，可能支持阿尔茨海默病可能是白细胞炎症-氧化状态外周改变的结果。
