Mestrado em Nanociências, Centro de Ciências Tecnológicas, Centro Universitário Franciscano, Santa Maria, CEP 97010-032, RS, Brazil.
Behav Brain Res. 2012 Apr 21;230(1):100-7. doi: 10.1016/j.bbr.2012.01.055. Epub 2012 Feb 7.
The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.
本研究的目的是探讨 M-NC 对淀粉样蛋白β (25-35) 肽诱导的小鼠损伤的保护作用，作为评估其治疗 AD 潜在价值的第一步。此外，我们比较了 M-NC 与游离美洛昔康 (M-F) 的作用。将小鼠分为六组：（I）假手术组，（II）淀粉样蛋白β组，（III）M-NC 组，（IV）M-F 组，（V）M-NC+淀粉样蛋白β组和（VI）M-F+淀粉样蛋白β组。小鼠分别用 M-NC（5mg/kg，灌胃）、M-F（5mg/kg，灌胃）或空白纳米胶囊（B-NC）预处理。处理 30 分钟后，用淀粉样蛋白β肽（3nmol）或过滤水进行侧脑室注射。采用 Morris 水迷宫（MWM）（第 4-7 天）和跳下型被动回避（SDPA）（第 7-8 天）任务评估学习和记忆能力。在实验方案结束时（第 8 天），处死动物并取出大脑进行生化测定（活性物质（RS）、非蛋白巯基（NPSH）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、谷胱甘肽 S-转移酶（GST））和组织学检查。我们的结果证实，淀粉样蛋白β肽导致小鼠学习和记忆障碍。组织学分析表明，淀粉样蛋白β肽导致神经元丢失、细胞堆积和染色质溶解。此外，本研究表明，接受淀粉样蛋白β肽的小鼠氧化应激增加。本研究的一个重要发现是 M-NC 对淀粉样蛋白β肽诱导的损伤具有保护作用。然而，M-F 没有保护作用。综上所述，本研究结果清楚地表明，载美洛昔康的聚合物纳米胶囊可防止学习和记忆障碍、神经元丢失和氧化应激，减轻由淀粉样蛋白β肽诱导的 AD 小鼠模型的损伤。
