Nishida J, McCuskey R S, McDonnell D, Fox E S
Department of Anatomy, College of Medicine, University of Arizona, Tucson 85724.
Am J Physiol. 1994 Dec;267(6 Pt 1):G1135-41. doi: 10.1152/ajpgi.1994.267.6.G1135.
Nitric oxide (NO) has been reported to have a protective function in attenuating hepatic injury during endotoxemia or sepsis. As a result, the role of NO in attenuating the hepatic microcirculatory alterations associated with endotoxemia was investigated in mice by in vivo microscopy. The livers were examined 2 h after intravenous injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS) alone or in combination with inhibitors of the synthesis of NO, NG-nitro-L-arginine methyl ester or NG-monomethyl-L-arginine. In the animals treated with the combination of NO synthase inhibitors and LPS, leukocyte adherence was increased threefold above that in animals treated with LPS alone. This was accompanied by a 33% reduction in sinusoidal blood flow. Simultaneous administration of L-arginine, but not D-arginine, eliminated these microcirculatory disturbances. The results demonstrate that inhibition of LPS-stimulated NO production results in an early hepatic microvascular inflammatory response to a dose of endotoxin which by itself is scarcely inflammatory. This suggests that NO plays a significant role in stabilizing the hepatic microcirculation during endotoxemia, thereby helping to protect the liver from ischemia and leukocyte-induced oxidative injury.
据报道，一氧化氮（NO）在减轻内毒素血症或脓毒症期间的肝损伤方面具有保护作用。因此，通过体内显微镜技术在小鼠中研究了NO在减轻与内毒素血症相关的肝微循环改变中的作用。在静脉注射单独的大肠杆菌0111:B4脂多糖（LPS）或与NO合成抑制剂NG-硝基-L-精氨酸甲酯或NG-单甲基-L-精氨酸联合注射2小时后检查肝脏。在用NO合酶抑制剂和LPS联合处理的动物中，白细胞黏附比单独用LPS处理的动物增加了两倍。这伴随着肝血窦血流减少33%。同时给予L-精氨酸而非D-精氨酸可消除这些微循环紊乱。结果表明，抑制LPS刺激的NO产生会导致对一定剂量内毒素的早期肝微血管炎症反应，而该剂量的内毒素本身几乎没有炎症性。这表明NO在稳定内毒素血症期间的肝微循环中起重要作用，从而有助于保护肝脏免受缺血和白细胞诱导的氧化损伤。
