HEPARIN-RELEASED SUPEROXIDE-DISMUTASE INHIBITS POSTISCHEMIC LEUKOCYTE ADHESION TO VENULAR ENDOTHELIUM
HEPARIN-RELEASED SUPEROXIDE-DISMUTASE INHIBITS POSTISCHEMIC LEUKOCYTE ADHESION TO VENULAR ENDOTHELIUM
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DOI：
10.1152/ajpheart.1994.267.3.h925
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发表时间：
1994-09-01
影响因子：
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通讯作者：
LEHR, HA
中科院分区：
文献类型：
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作者：
BECKER, M;MENGER, MD;LEHR, HA
缺血组织再灌注过程中形成的超氧自由基已被确定为缺血后组织损伤微血管表现的关键介质。这一理解基于对实验动物的研究，其中发现高剂量的超氧化物歧化酶（SOD；2.0-25.0 mg/kg 体重 iv）可抑制缺血后白细胞粘附以及液体和大分子的渗漏。使用仓鼠背侧皮褶室模型，我们现在证明，通过用显着较低剂量的外源性 CuZn-SOD（0.25 mg/kg 体重）或肝素（2,000 IU/kg 体重）对动物进行预处理，可以防止横纹肌缺血 4 小时后再灌注诱导的白细胞粘附到小静脉内皮，从而诱导 SOD 血浆相应增加通过从内皮细胞结合位点释放内源性细胞外 SOD 来发挥活性。这种保护作用一直维持到再灌注后24小时。相比之下，CuZn-SOD或肝素未能减弱营养性毛细血管灌注的缺血后关闭，这种现象是由于缺血诱导的内皮细胞肿胀，而不是由于再灌注相关事件，因此不易受到针对再灌注阶段产生的氧自由基的策略的影响。这项研究的结果 1) 意味着缺血后白细胞/内皮相互作用可以通过低剂量且临床上更相关的 SOD 来减弱，2) 在实验性缺血/再灌注损伤或其他氧自由基依赖性病理机制的研究中，注意在实验动物中使用肝素（即保持导管畅通）。
Superoxide radicals formed during reperfusion of ischemic tissues have been identified as a key mediator in the microvascular manifestations of postischemic tissue damage. This understanding is based on studies in laboratory animals in which high doses of superoxide dismutase (SOD; 2.0-25.0 mg/kg body wt iv) were found to inhibit postischemic leukocyte adhesion and the leakage of fluid and macromolecules. Using a dorsal skinfold chamber model in hamsters, we demonstrate now that protection from reperfusion-induced leukocyte adhesion to venular endothelium after 4 h of ischemia to striated muscle can be attained by pretreatment of the animals with a significantly lower dose of exogenous CuZn-SOD (0.25 mg/kg body wt) or with heparin (2,000 IU/kg body wt), which induces a comparable increase in SOD plasma activity through the release of endogenous extracellular SOD from endothelial cell binding sites. This protective effect was maintained until 24 h after reperfusion. In contrast, CuZn-SOD or heparin failed to attenuate the postischemic shutdown of nutritional capillary perfusion, a phenomenon that is due to ischemia-induced endothelial cell swelling, rather than due to reperfusion-associated events, and hence is not susceptible to strategies directed against oxygen radicals generated during the reperfusion phase. The results of this study 1) imply that postischemic leukocyte/endothelium interaction can be attenuated by a low and clinically more relevant dose of SOD, and 2) caveat the administration of heparin in laboratory animals (i.e., to keep catheters patent) in studies of experimental ischemia/reperfusion injury or other oxygen radical-dependent pathomechanisms.