Seekamp A, Mulligan M S, Till G O, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Am J Pathol. 1993 Apr;142(4):1217-26.
Ischemia followed by reperfusion in rat limb results in evidence of vascular injury in the limb as well as in the lung as measured by leakage of [125I]albumin and extravasation of [51Cr] red blood cells. Vascular injury in lung and limb was proportional to the time of limb reperfusion and was associated with accumulation of myeloperoxidase, as well as evidence of complement consumption. In this model, the rank order of protective interventions was: neutrophil depletion > catalase + superoxide dismutase = allopurinol > dimethylthiourea = dimethylsulfoxide > deferoxamine = complement depletion. These data suggest that toxic oxygen products of neutrophils are related to the development of vascular injury. There was a reasonable correlation between protective effects of interventions and reduced tissue content of myeloperoxidase. Systemic treatment with the L-arginine antagonists, NG-monomethyl-L-arginine or nitro-L-arginine methyl ester, was also protective against vascular injury, suggesting that metabolic products of L-arginine participate in events leading to injury.
大鼠肢体缺血再灌注会导致肢体以及肺部出现血管损伤迹象，这可通过[125I]白蛋白渗漏和[51Cr]红细胞外渗来衡量。肺部和肢体的血管损伤与肢体再灌注时间成正比，且与髓过氧化物酶的积累以及补体消耗迹象有关。在该模型中，保护性干预措施的效果排序为：中性粒细胞耗竭＞过氧化氢酶 + 超氧化物歧化酶 = 别嘌呤醇＞二甲基硫脲 = 二甲基亚砜＞去铁胺 = 补体耗竭。这些数据表明，中性粒细胞产生的毒性氧产物与血管损伤的发生有关。干预措施的保护作用与髓过氧化物酶组织含量降低之间存在合理的相关性。用L-精氨酸拮抗剂NG-单甲基-L-精氨酸或硝基-L-精氨酸甲酯进行全身治疗，对血管损伤也有保护作用，这表明L-精氨酸的代谢产物参与了导致损伤的过程。
