Takeda Y, Hashimoto H, Kosaka F, Hirakawa M, Inoue M
Department of Anesthesiology and Resuscitology, Okayama Medical School, Japan.
Am J Physiol. 1993 May;264(5 Pt 2):H1708-15. doi: 10.1152/ajpheart.1993.264.5.H1708.
To test the possible involvement of superoxide radicals in the pathogenesis of reperfusion injury, we synthesized a superoxide dismutase (SOD) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalently linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protective effects of SM-SOD on regional cerebral blood flow, intracranial pressure, cardiac index, vascular permeability, and neurological outcome were investigated using a model of global brain ischemia in dogs. Intra-arterial injection of SM-SOD (10 mg/kg) just before reperfusion increased reactive hyperemia (SM-SOD, 160 +/- 36 ml.100 g-1.min-1, means +/- SD, n = 6; control, 100 +/- 34 ml.100 g-1.min-1, n = 6, P = 0.015), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 +/- 14 ml.100 g-1.min-1; control 17 +/- 6 ml.100 g-1.min-1, P = 0.003), vascular permeability, and neurological outcome without affecting the cardiac index. These results indicate that superoxide radicals and/or their metabolite(s) might play a critical role in the pathogenesis of reperfusion injury in the brain.
为了测试超氧阴离子自由基在再灌注损伤发病机制中的可能作用，我们合成了一种超氧化物歧化酶（SOD）衍生物[与SOD共价连接的聚（苯乙烯 - 马来酸）丁酯（SM）]，它与白蛋白结合循环，具有延长的体内半衰期，并在pH降低的组织中蓄积。使用犬全脑缺血模型研究了SM-SOD对局部脑血流量、颅内压、心脏指数、血管通透性和神经功能结局的保护作用。再灌注前动脉内注射SM-SOD（10mg/kg）可增加反应性充血（SM-SOD，160±36ml·100g-1·min-1，均值±标准差，n = 6；对照组，100±34ml·100g-1·min-1，n = 6，P = 0.015），改善延迟性低灌注（缺血后7小时：SM-SOD，40±14ml·100g-1·min-1；对照组17±6ml·100g-1·min-1，P = 0.003）、血管通透性和神经功能结局，而不影响心脏指数。这些结果表明，超氧阴离子自由基和/或其代谢产物可能在脑再灌注损伤的发病机制中起关键作用。
