Adkins W K, Taylor A E
Department of Physiology, University of South Alabama College of Medicine, Mobile 36688.
J Appl Physiol (1985). 1990 Dec;69(6):2012-8. doi: 10.1152/jappl.1990.69.6.2012.
This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R.
本研究评估了缺血再灌注（I-R）对离体兔肺肺毛细血管通透性的影响，以及黄嘌呤氧化酶（XO）、醛氧化酶（AO）和中性粒细胞（PMN）在导致这种肺损伤中的作用。通过富含钨的饮食（0.7 g/kg）使XO和AO失活，用别嘌呤醇（100 microM）抑制XO或用甲萘醌（3.5 microM）抑制AO来研究XO和AO的作用。通过用单克隆抗体IB4（10 microM）阻止内皮细胞黏附来研究PMN的作用。在所有实验条件下，通过测定缺血再灌注前后的毛细血管滤过系数（Kf,c）来评估血管通透性。缺血2小时后的再灌注显著增加了肺毛细血管通透性（Kf,c从0.096±0.014变为0.213±0.025 ml·min-1·cmH2O-1·100 g-1），并且在再灌注时加入过氧化氢酶（50,000 U）可阻止这种增加（基线Kf,c为0.125±0.023和0.116±0.014 ml·min-1·cmH2O-1·100 g-1）。用富含钨的饮食使XO失活以及用别嘌呤醇抑制XO可防止缺血再灌注后观察到的Kf,c增加（从0.183±0.030变为0.185±0.033以及从0.126±0.018变为0.103±0.005 ml·min-1·cmH2O-1·100 g-1）。抑制AO对缺血再灌注损伤无影响（Kf,c从0.108±0.011变为0.167±0.014 ml·min-1·cmH2O-1·100 g-1）。阻止PMN黏附可显著减轻与缺血再灌注相关的Kf,c变化（从0.112±0.032变为0.090±0.065 ml·min-1·cmH2O-1·100 g-1）。我们得出结论，XO和PMN黏附而非AO参与了与缺血再灌注相关的毛细血管通透性增加。
