Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
J Neuroimmunol. 2019 May 15;330:108-115. doi: 10.1016/j.jneuroim.2019.03.003. Epub 2019 Mar 6.
Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are beneficial in treating AD; however, no significant clinical effects have been shown. Furthermore, no study has investigated the efficacy of combining these agents for treating AD. This study sought to determine the effect of a combination of indomethacin and atorvastatin in the PrP-hAβPPswe/PS1 (APP/PS1) transgenic AD mouse model. Treatment with indomethacin and atorvastatin ameliorated impairments in spatial learning and memory, and the active avoidance response in APP/PS1 mice. Moreover, we found a suppression of Aβ plaques and decreased concentration of Aβ in the hippocampus of APP/PS1 mice following treatment. In addition, indomethacin and atorvastatin ameliorated abnormal cytokine secretion, lymphocyte subset disorder, and hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis imbalances in APP/PS1 mice. The combination of indomethacin and atorvastatin restored immune and neuroendocrine processes, attenuated pathologic changes and cognitive impairments in APP/PS1 transgenic mice, and could thus be a potential therapeutic agent for AD.
越来越多的证据表明，炎症可能会促使阿尔茨海默病（AD）的病理发展，并使其恶化。先前的研究表明，吲哚美辛或阿托伐他汀有益于 AD 的治疗；然而，并未显示出显著的临床效果。此外，尚无研究探讨联合使用这些药物治疗 AD 的疗效。本研究旨在确定吲哚美辛和阿托伐他汀联合应用于 PrP-hAβPPswe/PS1（APP/PS1）转基因 AD 小鼠模型的效果。吲哚美辛和阿托伐他汀的治疗改善了 APP/PS1 小鼠的空间学习和记忆以及主动回避反应的损伤。此外，我们发现治疗后 APP/PS1 小鼠海马区的 Aβ 斑块减少，Aβ 浓度降低。此外，吲哚美辛和阿托伐他汀改善了 APP/PS1 小鼠异常的细胞因子分泌、淋巴细胞亚群紊乱以及下丘脑-垂体-肾上腺（HPA）和下丘脑-垂体-性腺（HPG）轴失衡。吲哚美辛和阿托伐他汀的联合应用恢复了免疫和神经内分泌过程，减轻了 APP/PS1 转基因小鼠的病理变化和认知障碍，因此可能成为 AD 的一种潜在治疗药物。
