Chamulitrat W, Skrepnik N V, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orieans 70112-1393, USA.
Shock. 1996 Mar;5(3):217-22. doi: 10.1097/00024382-199603000-00009.
Reactive oxygen species have been implicated in the gastrointestinal pathogenesis of septic and endotoxic shock. The objective of this study was to investigate the role of inducible nitric oxide synthase during endotoxin-induced formation of oxidants by cells of the small intestine. After intravenous Escherichia coli lipopolysaccharide (LPS) (1 mg/kg) injection, nitric oxide production was measured as nitrosyl complex formation in the ileum using electron paramagnetic resonance spectroscopy. Oxidative stress biomarkers were determined as duodenal mucosal-reduced thiols, the ileal lipid peroxidation and luminal free radical production using spin trapping methodology. Demonstration of nitrosyl complex formation commenced at 3 h and diminished 24 h post-LPS. Mucosal thiol levels were decreased at 3, 6, 12, and 18 h post-LPS treatment. At these time point, the ileal lipid peroxidation also increased as did luminal formation of hydroxyl radical adduct. Nitric oxide synthase inhibitors reversed the elevation of hydroxyl radical formation and reversed the decrease in mucosal-reduced thiol levels in the LPS-treated rats. Our data indicate that nitric oxide or its oxidant product(s), such as peroxynitrite, contribute to oxidative injury in the small intestine of rats treated with endotoxin.
活性氧已被认为与脓毒症和内毒素休克的胃肠道发病机制有关。本研究的目的是探讨诱导型一氧化氮合酶在内毒素诱导小肠细胞形成氧化剂过程中的作用。静脉注射大肠杆菌脂多糖（LPS）（1mg/kg）后，使用电子顺磁共振光谱法测量回肠中一氧化氮的产生，以亚硝酰复合物的形成来衡量。使用自旋捕获方法，将氧化应激生物标志物确定为十二指肠黏膜还原型硫醇、回肠脂质过氧化和肠腔自由基产生。LPS注射后3小时开始出现亚硝酰复合物形成的证据，并在24小时后减少。LPS处理后3、6、12和18小时，黏膜硫醇水平降低。在这些时间点，回肠脂质过氧化以及羟基自由基加合物的肠腔形成也增加。一氧化氮合酶抑制剂可逆转LPS处理大鼠中羟基自由基形成的升高，并逆转黏膜还原型硫醇水平的降低。我们的数据表明，一氧化氮或其氧化产物，如过氧亚硝酸盐，会导致内毒素处理大鼠小肠的氧化损伤。
