Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity.
Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity.
复制标题
对乙酰氨基酚通过抗氧化活性减轻脂多糖引起的认知障碍
DOI：
10.1186/s12974-016-0781-6
复制
发表时间：
2017-01-21
影响因子：
9.3
通讯作者：
Mi WD
中科院分区：
文献类型：
--
作者：
Zhao WX;Zhang JH;Cao JB;Wang W;Wang DX;Zhang XY;Yu J;Zhang YY;Zhang YZ;Mi WD
大量证据表明，神经炎症和氧化应激在术后认知功能障碍（POCD）和其他进行性神经退行性疾病的病理生理中起重要作用。越来越多的证据表明，对乙酰氨基酚（APAP）具有不受重视的抗氧化和抗炎特性。然而，APAP对炎症和氧化应激的认知后遗症的影响尚不清楚。本研究旨在探讨APAP对脂多糖（lipopolysaccharide，LPS）诱导的小鼠认知功能障碍的神经保护作用。方法建立LPS诱导的小鼠认知功能障碍模型，观察APAP对LPS诱导的认知功能障碍的神经保护作用。成年C57 BL/6小鼠在脑室内微量注射LPS前半小时用APAP处理，此后每天用APAP处理，直到研究期结束。Morris水迷宫用于评估注射后第1天至第3天的认知功能。动物行为测试以及病理和生化分析进行评估LPS诱导的海马损伤和APAP的神经保护作用。ResultsLPS处理的小鼠表现出受损的性能在Morris水迷宫中，而不改变自发运动活动，这是改善与APAP治疗。APAP可抑制LPS诱导的海马区促炎细胞因子的积累和小胶质细胞的活化。此外，APAP还能提高海马SOD活性，降低MDA水平，调节糖原合成酶激酶3β（GSK 3 β）活性，并提高脑源性神经营养因子（BDNF）表达。此外，APAP显着降低Bax/Bcl-2比值和神经元凋亡在LPS-处理mice.ConclusionsOur结果表明，APAP可能具有神经保护作用，对LPS诱导的认知障碍和炎症和氧化应激通过其抗氧化和抗炎特性的机制，以及其抑制线粒体通透性转换（MPT）孔和随后的凋亡途径的能力。
BackgroundConsiderable evidence has shown that neuroinflammation and oxidative stress play an important role in the pathophysiology of postoperative cognitive dysfunction (POCD) and other progressive neurodegenerative disorders. Increasing evidence suggests that acetaminophen (APAP) has unappreciated antioxidant and anti-inflammatory properties. However, the impact of APAP on the cognitive sequelae of inflammatory and oxidative stress is unknown. The objective of this study is to explore whether APAP could have neuroprotective effects on lipopolysaccharide (LPS)-induced cognitive impairment in mice.MethodsA mouse model of LPS-induced cognitive impairment was established to evaluate the neuroprotective effects of APAP against LPS-induced cognitive impairment. Adult C57BL/6 mice were treated with APAP half an hour prior to intracerebroventricular microinjection of LPS and every day thereafter, until the end of the study period. The Morris water maze was used to assess cognitive function from postinjection days 1 to 3. Animal behavioural tests as well as pathological and biochemical assays were performed to evaluate LPS-induced hippocampal damage and the neuroprotective effect of APAP.ResultsMice treated with LPS exhibited impaired performance in the Morris water maze without changing spontaneous locomotor activity, which was ameliorated by treatment with APAP. APAP suppressed the accumulation of pro-inflammatory cytokines and microglial activation induced by LPS in the hippocampus. In addition, APAP increased SOD activity, reduced MDA levels, modulated glycogen synthase kinase 3β (GSK3β) activity and elevated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Moreover, APAP significantly decreased the Bax/Bcl-2 ratio and neuron apoptosis in the hippocampus of LPS-treated mice.ConclusionsOur results suggest that APAP may possess a neuroprotective effect against LPS-induced cognitive impairment and inflammatory and oxidative stress via mechanisms involving its antioxidant and anti-inflammatory properties, as well as its ability to inhibit the mitochondrial permeability transition (MPT) pore and the subsequent apoptotic pathway.