Nanetti Laura, Taffi Ruja, Vignini Arianna, Moroni Cinzia, Raffaelli Francesca, Bacchetti Tiziana, Silvestrini Mauro, Provinciali Leandro, Mazzanti Laura
Institute of Biochemistry, Università Politecnica delle Marche, Ancona, Italy.
Mol Cell Biochem. 2007 Sep;303(1-2):19-25. doi: 10.1007/s11010-007-9451-4. Epub 2007 Mar 30.
Oxidative stress is probably one of the mechanisms involved in neuronal damage induced by ischemia-reperfusion, and the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress. The aim of this study was to investigate the status of oxidative stress, NO and ONOO(-) levels in patients with atherothrombotic and lacunar acute ischemic stroke and iNOS, eNOS and nitrotyrosine expression in the same patients. Plasma ONOO(-) levels were significantly higher in patients than in controls while NO decreases in patients in respect to controls. Densitometric analysis of bands indicated that iNOS and N-Tyr protein levels were significantly higher in patients in respect to controls. This study has highlighted a significant NO decrease in our patients compared with controls and this is most probably due to the increased expression of inducible NO synthase by the effect of thrombotic attack. In fact, the constitutive NO isoforms, which produce small amounts of NO, are beneficial, while activation of the inducible isoform of NO, which produces much more NO, causes injury, being its toxicity greatly enhanced by generation of peroxynitrite. The significant ONOO(-) increase observed in our patients, compared to controls, is most probably due to reaction of NO with O(2)(*-) . These findings suggest that free radical production and oxidative stress in ischemic stroke might have a major role in the pathogenesis of ischemic brain injury. Peroxynitrite might be the main marker of brain damage and neurological impairment in acute ischemic stroke.
氧化应激可能是缺血再灌注诱导神经元损伤所涉及的机制之一，血浆的抗氧化活性可能是提供保护以抵御中风相关氧化应激所致神经损伤的一个重要因素。本研究的目的是调查动脉粥样硬化血栓形成性和腔隙性急性缺血性中风患者的氧化应激状态、一氧化氮（NO）和过氧亚硝酸盐（ONOO⁻）水平，以及同一患者中诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS）和硝基酪氨酸的表达。患者血浆中的ONOO⁻水平显著高于对照组，而患者的NO水平相对于对照组降低。条带的光密度分析表明，患者的iNOS和N-酪氨酸蛋白水平相对于对照组显著更高。本研究突出显示，与对照组相比，我们的患者中NO显著降低，这很可能是由于血栓形成攻击的作用导致诱导型一氧化氮合酶表达增加所致。事实上，产生少量NO的组成型NO同工型是有益的，而产生更多NO的诱导型NO同工型的激活会导致损伤，因为过氧亚硝酸盐的生成会大大增强其毒性。与对照组相比，我们的患者中观察到的ONOO⁻显著增加很可能是由于NO与超氧阴离子（O₂⁻*）反应所致。这些发现表明，缺血性中风中的自由基产生和氧化应激可能在缺血性脑损伤的发病机制中起主要作用。过氧亚硝酸盐可能是急性缺血性中风中脑损伤和神经功能障碍的主要标志物。
