Obayashi H, Koshi S, Miyauchi Y, Inoue M
Department of Surgery, Kumamoto University Medical School, Japan.
Proc Soc Exp Biol Med. 1991 Feb;196(2):164-9. doi: 10.3181/00379727-196-43173.
Although oxygen-free radicals have been postulated to play an important role in the pathogenesis of gastric mucosal injury induced by posthemorrhagic blood transfusion, direct evidence supporting this hypothesis is lacking. Superoxide dismutase (SOD) has been shown to inhibit oxygen toxicity in vitro in various types of cell injury. However, in some cases, oxidative tissue injury cannot be decreased efficiency predominantly due to its rapid elimination by renal glomerular filtration. To overcome such frustrating situations, we have synthesized a SOD derivative that circulates bound to albumin with a half-life of 6 hr. When blood was withdrawn from the rat (22 ml/kg) for 30 min followed by transfusion of the extracted blood, marked gastric mucosal lesions occurred within 30 min after transfusion. Intravenously injected SOD derivative markedly decreased gastric mucosal injury. Kinetic analysis using 125I-labeled albumin revealed that the vascular permeability of the stomach increased significantly after transfusion by a SOD derivative inhibitable mechanism. Thus, superoxide radical and/or its metabolite(s) play a critical role in the pathogenesis of posthemorrhagic transfusion-induced gastric injury.
尽管已有假设认为氧自由基在出血后输血所致胃黏膜损伤的发病机制中起重要作用，但缺乏支持这一假说的直接证据。超氧化物歧化酶（SOD）已被证明在体外能抑制各种类型细胞损伤中的氧毒性。然而，在某些情况下，氧化组织损伤并不能有效减轻，主要是因为它会被肾小球滤过迅速清除。为克服这种令人沮丧的情况，我们合成了一种与白蛋白结合循环的SOD衍生物，其半衰期为6小时。当从大鼠体内抽取血液（22毫升/千克）30分钟后再输回所抽取的血液时，输血后30分钟内出现明显的胃黏膜损伤。静脉注射SOD衍生物可显著减轻胃黏膜损伤。使用125I标记白蛋白的动力学分析表明，输血后胃的血管通透性通过一种可被SOD衍生物抑制的机制显著增加。因此，超氧自由基和/或其代谢产物在出血后输血所致胃损伤的发病机制中起关键作用。
