Nicotinamide inhibits nuclear factor-kappa B translocation after transient focal cerebral ischemia
Nicotinamide inhibits nuclear factor-kappa B translocation after transient focal cerebral ischemia
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DOI：
10.1097/ccm.0b013e31822f0b08
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发表时间：
2012-02-01
影响因子：
8.8
通讯作者：
Lee, E-Jian
中科院分区：
文献类型：
--
作者：
Chen, Tsung-Ying;Lin, Miao-Hui Sylvia;Lee, E-Jian
目的：探讨烟酰胺对实验性卒中的抗炎作用。设计：前瞻性实验室研究。地点：一所大学教学医院的研究实验室。对象：成年雄性SD大鼠(250g-300g)。干预：通过一组脱细胞检测和脂多糖刺激的RAW 264.7和BV2细胞，评价烟酰胺的抗氧化、清除自由基和抗炎作用。大鼠大脑中动脉短暂性闭塞90min。方法和主要结果：烟酰胺能有效地抑制脂多糖刺激的RAW 264.7和BV2细胞(p<；0.05)核因子-kappaB的转位和结合活性以及肿瘤坏死因子-α、亚硝酸盐/硝酸盐和白介素6的产生，但抗氧化和清除自由基的作用较弱。与对照组相比，烟酰胺处理组缺血脑中中性粒细胞和巨噬细胞/激活的小胶质细胞的浸润显著减少了53%和77%(p<；0.05)。此外，烟酰胺显著降低缺血脑组织中核因子-kappaB抑制蛋白的磷酸化、核因子-kappaB的转位和结合活性以及诱导型一氧化氮的合成(p<；0.05)。因此，烟酰胺有效地减少脑梗塞和改善神经行为结果，分别为43%和50%(p<；0.05)。结论：烟酰胺有效地抑制缺血后核因子-kappaB的激活，并显示出强大的抗炎作用。(CRET CARE Med 2012；40：532-537)
Objective: We explored the putative anti-inflammatory effects of nicotinamide against experimental stroke.Design: Prospective laboratory study.Setting: Research laboratory in a university teaching hospital.Subjects: Adult male Sprague-Dawley rats (250-300 g).Interventions: The antioxidant, radical scavenging, and anti-inflammatory actions of nicotinamide were evaluated using a panel of acellular assays and lipopolysaccharide-stimulated RAW 264.7 and BV2 cells. Animals were subjected to transient middle cerebral artery occlusion for 90 mins. Nicotinamide (500 mg/kg) or vehicle was given intravenously at reperfusion onset.Measurements and Main Results: Nicotinamide effectively inhibited nuclear factor-kappa B translocation and binding activity as well as the production of tumor necrosis factor-alpha, nitrite/nitrate, and interleukin-6 in the lipopolysaccharide-stimulated RAW 264.7 and BV2 cells (p < .05, respectively) but exhibited weak antioxidant and radical-scavenging actions. Relative to controls, nicotinamide-treated animals had significant reductions in neutrophil and macrophage/activated microglial infiltration in the ischemic brain by 53% and 77% (p < .05, respectively). Additionally, nicotinamide significantly attenuated phosphorylation of nuclear factor-kappa B's inhibitory protein, nuclear factor-kappa B translocation and binding activity, and the synthesis of inducible nitric oxide in the ischemic brain (p < .05, respectively). Consequently, nicotinamide effectively reduced brain infarction and improved neurobehavioral outcome by 43% and 50% (p < .05, respectively).Conclusions: Nicotinamide effectively attenuated post-ischemic nuclear factor-kappa] B activation and exhibited robust anti-inflammatory actions against ischemic stroke. (Crit Care Med 2012; 40:532-537)