Generation of reactive oxygen species by neutrophils and endothelial cell injury in normal and preeclamptic pregnancies
Generation of reactive oxygen species by neutrophils and endothelial cell injury in normal and preeclamptic pregnancies
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DOI：
10.1161/01.hyp.0000184197.11226.71
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发表时间：
2005-10-01
期刊：
影响因子：
8.3
通讯作者：
Nakano, H
中科院分区：
文献类型：
--
作者：
Tsukimori, K;Fukushima, K;Nakano, H
本研究的目的是探讨子痫前期患者胎盘来源的活性氧在内皮细胞功能障碍中的作用。我们首先评估了正常非妊娠妇女（n=10）、正常妊娠妇女（n=15）和先兆子痫妇女（n=12）中亚硝酸盐和超氧阴离子产生之间的相关性。然后，我们研究了嗜酸性粒细胞介导的氧自由基损伤人脐静脉内皮细胞在体外。通过细胞色素C还原测定神经元超氧化物释放;通过改良的Griess反应测定亚硝酸盐释放，通过Cr-51释放测定内皮细胞损伤。N-甲酰甲硫氨酰亮氨酰苯丙氨酸刺激的中性粒细胞释放的超氧化物显着增加，与其他2组相比，先兆子痫的妇女。与正常妊娠相比，子痫前期患者中性粒细胞亚硝酸盐释放量显著降低。当中性粒细胞用超氧化物歧化酶预处理时，正常妊娠和先兆子痫患者中性粒细胞释放的亚硝酸盐没有差异，表明先兆子痫患者过量的超氧阴离子可通过中性粒细胞自分泌功能降低一氧化氮的生物利用度。先兆子痫组中性粒细胞介导的内皮细胞损伤明显高于其他两组。过氧化氢在子痫前期中嗜酸性粒细胞介导的内皮细胞损伤中起重要作用，因为过氧化氢酶抑制内皮细胞损伤。当中性粒细胞用N-G-硝基-L-精氨酸甲酯预处理时，子痫前期中嗜中性粒细胞介导的内皮细胞损伤减少，表明过氧亚硝酸盐形成作为内皮细胞损伤机制的作用。总之，调节中性粒细胞导致超氧化物产生占主导地位的亚硝酸盐释放提供了一个合理的解释先兆子痫的内皮细胞功能障碍。
The aim of this study was to investigate the role of neutrophil-derived reactive oxygen species on endothelial cell dysfunction in preeclampsia. We first assessed the correlation between nitrite and superoxide anion production in normal nonpregnant (n=10), normal pregnant (n=15), and preeclamptic women (n=12). We then examined neutrophil-mediated oxygen radical damage to human umbilical vein endothelial cells in vitro. Neutrophil superoxide release was measured by cytochrome C reduction; nitrite release was measured by the modified Griess reaction, and endothelial cell injury was measured by Cr-51 release. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide release by neutrophils was significantly increased in women with preeclampsia compared with the other 2 groups. Nitrite release by neutrophils was significantly decreased in preeclampsia compared with normal pregnancy. When neutrophils were pretreated with superoxide dismutase, nitrite release by neutrophils did not differ between normal pregnancy and preeclampsia, suggesting that excess superoxide anion in preeclampsia could reduce bioavailability of nitric oxide through neutrophil autocrine function. Neutrophil-mediated endothelial cell injury was significantly greater in women with preeclampsia than in the other 2 groups. Hydrogen peroxide was important in neutrophil-mediated endothelial cell injury in preeclampsia as catalase inhibited endothelial cell injury. When neutrophils were pretreated with N-G-nitro-L-arginine methyl ester, neutrophil-mediated endothelial cell injury in preeclampsia was decreased, indicating a role for peroxynitrite formation as a mechanism of endothelial cell injury. In conclusion, the modulation of neutrophils causing superoxide production to dominate over nitrite release provides a reasonable explanation for endothelial cell dysfunction in preeclampsia.