Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 1277 Jiefang Avenue, Wuhan, Hubei, China.
J Mol Neurosci. 2012 Jan;46(1):153-61. doi: 10.1007/s12031-011-9541-3. Epub 2011 May 17.
Aspirin (ASA) is one of the most widely used nonsteroidal anti-inflammatory drugs. ASA has primarily been used to treat headaches, rheumatic pain, and inflammation, but its therapeutic effects have recently been demonstrated on a range of disorders, including those of the central nervous system. In this study, we investigated whether ASA is neuroprotective in inflammation-mediated neurodegenerative diseases. Pretreatment with ASA reduced the lipopolysaccharide (LPS)-induced degeneration of dopaminergic (DA) neurons in mesencephalic neuron-glia cultures in a dose-dependent manner. The neuroprotective effect of ASA was attributed to the inhibition of microglial activation because of its observed inhibitory effects on LPS-stimulated nitric oxide, tumor necrosis factor-α, and superoxide production by microglial cells. Moreover, ASA increased the production of the anti-inflammatory cytokines transforming growth factor beta-1 and interleukin-10 in neuron-glia cultures after stimulation with LPS. Mechanistic studies revealed that the neuroprotective effects of ASA were mediated through the inhibition of nicotinamide adenine dinucleotide phosphate oxidase (PHOX), a key enzyme for superoxide production in microglia. These results suggest that ASA protects DA neurodegeneration by inhibiting the microglial-mediated oxidative stress/inflammatory response and by regulating the production of anti-inflammatory cytokines.
阿司匹林（ASA）是最广泛使用的非甾体类抗炎药之一。ASA 主要用于治疗头痛、风湿痛和炎症，但最近的研究表明它对一系列疾病具有治疗作用，包括中枢神经系统疾病。在本研究中，我们研究了 ASA 是否对炎症介导的神经退行性疾病具有神经保护作用。ASA 的预处理以剂量依赖性方式减少了中脑神经-胶质细胞培养物中脂多糖（LPS）诱导的多巴胺能（DA）神经元变性。ASA 的神经保护作用归因于其对 LPS 刺激的小胶质细胞中一氧化氮、肿瘤坏死因子-α和超氧化物产生的抑制作用，从而抑制小胶质细胞的激活。此外，ASA 增加了神经元-胶质细胞培养物中 LPS 刺激后抗炎细胞因子转化生长因子β-1 和白细胞介素-10 的产生。机制研究表明，ASA 的神经保护作用是通过抑制烟酰胺腺嘌呤二核苷酸磷酸氧化酶（PHOX）介导的，PHOX 是小胶质细胞中超氧化物产生的关键酶。这些结果表明，ASA 通过抑制小胶质细胞介导的氧化应激/炎症反应和调节抗炎细胞因子的产生来保护 DA 神经退行性变。
