Free radical-mediated reperfusion injury: a selective review.
Free radical-mediated reperfusion injury: a selective review.
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发表时间：
1987-06
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通讯作者：
G. Bulkley
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作者：
G. Bulkley
局部缺血引起的组织损伤是工业化社会中的主要医学问题。尽管传统观点将这种损伤过程归因于缺血本身，但最近的研究发现，损伤的一个变量，但通常相当大的比例是由再灌注时黄嘌呤氧化酶产生的有毒氧代谢物引起的。该机制首先在猫小肠中中度轻度部分血管闭塞模型中鉴定和表征。惊人的相似机制随后被证实为胃、胰腺、肝脏、皮肤、骨骼肌、心脏、肺、肾脏和中枢神经系统中缺血/再灌注损伤的基础。这一概念的临床应用潜力主要与由于这种再灌注机制引起的总缺血后损伤的比例相关，而不是由于缺血本身引起的比例。具有讽刺意味的是，在肠缺血的临床病例中，再灌注成分似乎比例很小，并且治疗缺血性肠病的潜力相应地受到限制。另一方面，有理由预期，可以通过无毒手段容易地实现的自由基介导的再灌注损伤的消融，可以为缺血性肾病、心肌梗死、中风、心脏骤停的治疗以及为移植保存的器官的治疗提供实质性益处。
Tissue damage as a consequence of ischemia is a major medical problem in an industrialized society. Whereas the conventional view has attributed this injury process to ischemia itself, recent studies have found that a variable, but often substantial proportion of the injury is caused by toxic oxygen metabolites that are generated from xanthine oxidase at the time of reperfusion. This mechanism was first identified and characterized in a model of moderately mild partial vascular occlusion in the feline small intestine. Strikingly similar mechanisms have been subsequently confirmed as the basis for ischemia/reperfusion injury in the stomach, pancreas, liver, skin, skeletal muscle, heart, lung, kidney and central nervous system. The potential for clinical application of this concept is related primarily to that proportion of the total post-ischemic injury that is due to this reperfusion mechanism, set against the proportion due to ischemia itself. Ironically, in clinical cases of intestinal ischemia the reperfusion component appears to be proportionately small, and the potential for treatment of ischemic bowel disease is correspondingly limited. On the other hand, there is reason to expect that the ablation of free radical-mediated reperfusion injury, something that can be readily achieved through non-toxic means, may provide substantial benefit for the treatment of ischemic renal disease, myocardial infarction, stroke, cardiac arrest, and of organs preserved for transplantation.