Harbrecht B G, Billiar T R, Stadler J, Demetris A J, Ochoa J, Curran R D, Simmons R L
Department of Surgery, University of Pittsburgh, Pennsylvania.
J Leukoc Biol. 1992 Oct;52(4):390-4. doi: 10.1002/jlb.52.4.390.
Corynebacterium parvum-treated mice produce large amounts of circulating nitrogen oxides and develop a severe liver injury in response to lipopolysaccharide (LPS). Concurrent administration of NG-monomethyl-L-arginine not only suppresses nitric oxide synthesis in these animals but also profoundly increases the hepatic damage following LPS. In this report, we present evidence that the increased hepatic damage from inhibition of nitric oxide synthesis is mediated in part by superoxide and hydroxyl radicals. The hepatic damage induced by suppressing nitric oxide production during endotoxemia could be reduced by treating mice with superoxide dismutase and deferoxamine, scavengers of superoxide and hydroxyl radicals, respectively. This damage could also be prevented by treating mice with the anticoagulant heparin sodium. The results suggest that nitric oxide synthesis during endotoxemia is important in preventing hepatic damage by reducing oxygen radical-mediated hepatic injury and preventing intravascular thrombosis.
经短小棒状杆菌处理的小鼠会产生大量循环性氮氧化物，并在接触脂多糖（LPS）时出现严重肝损伤。同时给予NG-单甲基-L-精氨酸不仅会抑制这些动物体内的一氧化氮合成，还会显著加重LPS诱导后的肝损伤。在本报告中，我们提供证据表明，一氧化氮合成受抑制后肝损伤增加部分是由超氧阴离子和羟自由基介导的。在内毒素血症期间，通过分别用超氧化物歧化酶和去铁胺（超氧阴离子和羟自由基的清除剂）处理小鼠，可以减轻因抑制一氧化氮合成而导致的肝损伤。用抗凝剂肝素钠处理小鼠也可以预防这种损伤。结果表明，内毒素血症期间的一氧化氮合成对于通过减少氧自由基介导的肝损伤和预防血管内血栓形成来防止肝损伤很重要。
