Siesjö B K, Agardh C D, Bengtsson F
Laboratory for Experimental Brain Research, Lund University Hospital, Sweden.
Cerebrovasc Brain Metab Rev. 1989 Fall;1(3):165-211.
Although free radicals have been suggested to contribute to ischemic brain damage for more than 10 years, it is not until quite recently that convincing evidence has been presented for their involvement in both sustained and transient ischemia. The hypothesis is examined against current knowledge of free radical chemistry, as it applies to biological systems, and of cellular iron metabolism. It is emphasized that those advents have changed our outlook on free radical-induced tissue damage. First, it has been realized that damage to DNA and proteins may be an earlier event than lipid peroxidation, perhaps also a more important one. Second, evidence now exists that the triggering event in free radical-induced damage is a disturbance of cellular iron metabolism, notably delocalization of protein-bound iron, and its chelation by compounds that trigger site-specific free radical damage. Third, methods have been developed that allow the demonstration of partially induced oxygen species in tissues, and scavengers have become available that can curb free radical reactions. As a result of these events, it has been possible to demonstrate formation of free radicals in oxygen toxicity, trauma, and ischemia, and their participation in the cell damage that is incurred in these conditions, particularly in causing vascular pathology and edema. It is suggested that in ischemia, free radical damage becomes pathogenetically important when the ischemia is of long duration, when conditions favor continued delivery of some oxygen to the ischemic tissue, and particularly when such partially oxygen-deprived tissue is reoxygenated.
尽管自由基被认为与缺血性脑损伤有关已有十多年，但直到最近才出现令人信服的证据表明它们参与了持续性和短暂性缺血。本文根据自由基化学（适用于生物系统）和细胞铁代谢的现有知识对这一假说进行了检验。需要强调的是，这些进展改变了我们对自由基诱导组织损伤的看法。首先，人们已经认识到，对DNA和蛋白质的损伤可能比脂质过氧化更早发生，也许也更重要。其次，现在有证据表明，自由基诱导损伤的触发事件是细胞铁代谢紊乱，特别是蛋白质结合铁的离域化，以及它被触发位点特异性自由基损伤的化合物螯合。第三，已经开发出能够证明组织中部分诱导的氧物种的方法，并且有了可以抑制自由基反应的清除剂。由于这些进展，已经有可能证明在氧中毒、创伤和缺血中自由基的形成，以及它们参与这些情况下发生的细胞损伤，特别是在导致血管病变和水肿方面。有人提出，在缺血时，当缺血持续时间长、条件有利于向缺血组织持续输送一些氧气时，特别是当这种部分缺氧的组织再灌注时，自由基损伤在发病机制上变得很重要。
