Dynamics of nitric oxide (NO) in biological miliue and mechanism of NO-induced injury.

越来越多的证据表明，NO具有极其多样的生物学功能，但由于其寿命短、浓度低，在生物系统中的动力学尚不清楚。此外，NO的细胞毒性机制尚未阐明。本研究的目的是1)研究NO和超氧化物的反应，因为它们以扩散受限的速度相互反应，形成过氧亚硝酸根。所有这些都是有效的细胞毒性分子。2)用体外培养细胞和大鼠体内系统测定NO、超氧化物和过氧亚硝酸根的产生。3)在内毒素休克或慢性变应性鼻炎患者中，通过测量硝基酪氨酸的生成作为过氧亚硝酸根损伤的足迹，来说明过氧亚硝酸根在疾病中的作用。结果1)在这些NO合酶(bNOS，iNOS，eNOS)中，iNOS的NO通量最快。2)NO合成酶成功地产生了超氧化物，并阐明了NOS中电子流动的动力学。3)内毒素休克或变应性鼻炎患者存在硝基酪氨酸的形成。

An increasing evidence shows extreamely diverse biological functions of NO.However its dynamics in bIological system is not clealy defined due to its short life and low concentration. Furthermore the mechanism of cytotoxic aspect of NO has not been elucidated.The purposes of this study were 1) to examine the reaction of NO and superoxide since both react each other at a diffusion-limited rate and form peroxynitrite. All of these are potent cytotoxic molecules. 2) to measure productions of NO, superoxide and peroxynitrite in in vitro system using culture cells and in in vivo system using rats. And 3) to demonstrate the role of peroxynitrite in diseases by measuring nitrotyrosine formation as a footprint of peroxynitrite-induced injury in patients who are suffering from endotoxin shock or from chronic allergic rhinitis.Results1) Among these NO synthase (bNOS, iNOS, eNOS) the flux of NO from INOS is the most rapid.2) The generation of superoxide from NO synthases was successful and the kinetics of electron flow in the NOS were clarified.3) Nitrotyrosine formation was demonstrated in patients with endotoxin shock or allergic rhinitis.