Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury
Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury
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DOI：
10.1161/01.str.0000245116.40163.1c
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发表时间：
2006-11-01
期刊：
影响因子：
8.3
通讯作者：
Roh, Jae-Kyu
中科院分区：
文献类型：
--
作者：
Jung, Keun-Hwa;Chu, Kon;Roh, Jae-Kyu
背景和目的-亚硝酸盐生成一氧化氮 (NO) 的速率与氧气和 pH 水平的降低呈线性关系。最近，据报道，亚硝酸盐衍生的一氧化氮对肝脏和心脏缺血再灌注损伤具有深远的保护作用。本研究假设亚硝酸盐在缺血脑中会被还原为NO并发挥NO依赖的神经保护作用。方法采用腔内线栓塞成年雄性大鼠大脑中动脉诱导脑缺血再灌注损伤。再灌注时静脉注射亚硝酸钠溶液。输注硝酸钠和直接NO清除剂羧基PTIO（缺血手术前30分钟）进行比较。结果-亚硝酸盐减少了梗塞体积，增强了局部脑血流量和功能恢复。在 48 nmol 和 480 nmol 浓度下观察到该效应，但在 4800 nmol 亚硝酸盐和 480 nmol 硝酸盐浓度下未观察到该效应。亚硝酸盐的神经保护作用被羧基-PTIO 完全抑制。 480 nmol 亚硝酸盐减弱了缺血脑中的二氢乙锭活性、3-硝基酪氨酸形成和脂质过氧化。结论-亚硝酸盐在缺血脑中发挥了深远的神经保护作用和抗氧化特性。这些结果表明，亚硝酸盐作为 NO 的生物储存储备，可能是急性中风的新型治疗剂。
Background and Purpose-The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects.Methods-Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons.Results-Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain.Conclusions-Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.