THE ROLE OF OXYGEN-DERIVED FREE-RADICALS IN ISCHEMIA-INDUCED INCREASES IN CANINE SKELETAL-MUSCLE VASCULAR-PERMEABILITY
THE ROLE OF OXYGEN-DERIVED FREE-RADICALS IN ISCHEMIA-INDUCED INCREASES IN CANINE SKELETAL-MUSCLE VASCULAR-PERMEABILITY
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DOI：
10.1161/01.res.57.4.599
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发表时间：
1985-01-01
影响因子：
20.1
通讯作者：
TAYLOR, AE
中科院分区：
文献类型：
--
作者：
KORTHUIS, RJ;GRANGER, DN;TAYLOR, AE
以前的研究表明，血管通透性增加骨骼肌受到4小时的流入闭塞。然而，渗透性增加的潜在机制尚不清楚。本研究的目的是评估的作用，氧衍生的自由基和组胺作为假定的介质增加的渗透性骨骼肌进行4小时的流入闭塞。在以下条件下，估计犬股薄肌中总血浆蛋白的渗透反射系数和等重毛细血管压：对照、缺血和缺血加别嘌呤醇预处理（黄嘌呤氧化酶抑制剂），过氧化氢酶（一种过氧化物酶，可将过氧化氢还原为水和分子氧）、超氧化物歧化酶（超氧阴离子清除剂）、二甲亚砜（羟基自由基清除剂）、苯海拉明（组胺H1-受体阻断剂）或西咪替丁（组胺H2-受体阻断剂）。缺血，然后再灌注，显着降低反射系数从0.94 ±。0.02至0.64 . ±. 0.02和等重毛细管压力从13.8 ±. 1.0 mm Hg至6.9 . ±. 0.4 mmHg，表明微血管通透性显著增加。先前用苯海拉明或西咪替丁治疗并没有显著改变由缺血引起的渗透性增加。然而，预处理别嘌呤醇，过氧化氢酶，超氧化物歧化酶，或二甲亚砜显着减弱血管通透性的增加。这项研究的结果表明，氧自由基是主要负责增加血管通透性产生的缺血-再灌注，羟基自由基可能是主要的破坏性自由基，黄嘌呤氧化酶可能是主要来源的氧衍生自由基在缺血骨骼肌。
Previous studies indicate that vascular permeability is increased in skeletal muscle subjected to 4 hours of inflow occlusion. However, the mechanism(s) underlying the increase in permeability are unknown. The aim of this study was to assess the role of oxygen-derived free radicals and histamine as putative mediators of the increased permeability in skeletal muscle subjected to 4 hours of inflow occlusion. The osmotic reflection coefficient for total plasma proteins and isogravimetric capillary pressure were estimated in canine gracilis muscle for the following conditions: control, ischemia, and ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), catalase (a peroxidase that reduces hydrogen peroxide to water and molecular oxygen), superoxide dismutase (a superoxide anion scavenger), dimethyl sulfoxide (a hydroxyl radical scavenger), diphenhydramine (a histamine H1-receptor blocker), or cimetidine (a histamine H2-receptor blocker). Ischemia, followed by reperfusion, significantly reduced the reflection of coefficient from 0.94 .+-. 0.02 to 0.64 .+-. 0.02 and isogravimetric capillary pressure from 13.8 .+-. 1.0 mm Hg to 6.9 .+-. 0.4 mmHg, indicating a dramatic increase in microvascular permeability. Prior treatment with diphenhydramine or cimetidine did not significantly alter the permeability increase induced by ischemia. However, pretreatment with allopurinol, catalase, superoxide dismutase, or dimethylsulfoxide did significantly attenuate the increase in vascular permeability. The results of this study indicate that oxygen radicals are primarily responsible for the increased vascular permeability produced by ischemia-reperfusion, that the hydroxyl radical may represent the primary damaging radical, and that xanthine oxidase may represent the primary source of oxygen-derived free radicals in ischemic skeletal muscle.