A kinetic study on functional impairment of nitric oxide-exposed rat erythrocytes.
A kinetic study on functional impairment of nitric oxide-exposed rat erythrocytes.
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一项关于一氧化氮暴露大鼠红细胞功能障碍的动力学研究。
DOI：
10.1289/ehp.8773171
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发表时间：
1987-08
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
在大鼠体内急性暴露于25~250ppm的一氧化氮(NO)时，根据实验数据(借助计算机模拟)估计了亚硝酸血红蛋白(Hb-NO)和高铁血红蛋白(MetHb)形成的动力学参数。同时检测红细胞的生化和流变学损伤。比较了Hb-NO和MetHb在血液中生成的时间进程，并与简化动力学模型模拟的时间进程进行了比较。从Hb-NO生成MetHb的速度远快于MetHb还原为亚铁形式和解离Hb-NO的速度，因此，MetHb含量始终大于Hb-NO含量。大鼠暴露于高浓度NO后，MetHb还原活性下降，但置于清洁空气中后，其活性恢复正常。血液流变学上，血液粘度变化不大，但在高切应力下可见少量未变形细胞。形态上可见不同程度的棘细胞转化。在生物化学方面，大鼠红细胞暴露于高浓度NO后，未检测到膜蛋白的交联和膜磷脂的酰基链组成的改变，但在体外高浓度的NO暴露下，膜蛋白和血红蛋白之间发生了显著的氧化交联。总之，无论是对于持续性高铁血红蛋白血症还是对于膜损伤，维持红细胞的还原活性是保护NO诱导的氧化损伤的最重要的决定因素。
In acute in vivo exposure of rats to 25 to 250 ppm nitric oxide (NO) by use of a small exposure chamber for a single rat, the kinetic parameters of nitrosylhemoglobin (Hb-NO) and methemoglobin (MetHb) formation were estimated (with the aid of computer simulation) on the basis of experimental data. The biochemical and rheological injuries of erythrocytes were also examined. The time course of Hb-NO and MetHb formation in blood was compared with that simulated by a simplified kinetic model. The rate of MetHb formation from Hb-NO was much faster than MetHb reduction to ferrous form and dissociation of Hb-NO; thus, MetHb content was always greater than Hb-NO content. The activity of MetHb reduction decreased on exposure to a high concentration of NO, but the activity was recovered when rats were placed in clean air. Rheologically, the blood viscosity was scarcely altered, but a few undeformed cells were detected at high shear stress. Morphologically, echinocytic transformation was observed to some extent. Biochemically, the crosslinking of membrane proteins and the alteration of acyl chain composition of membrane phospholipids were not detected in the in vivo exposure, though the in vitro exposure of rat erythrocytes to high concentrations of NO revealed remarkable oxidative crosslinking among membrane proteins and hemoglobin. In conclusion, both for persistent methemoglobinemia and for membrane damage, the maintenance of reductive activity in erythrocytes is the most important determinant factor for the protection of NO-induced oxidative injury.