GUT ISCHEMIA MEDIATES LUNG INJURY BY A XANTHINE OXIDASE-DEPENDENT NEUTROPHIL MECHANISM
GUT ISCHEMIA MEDIATES LUNG INJURY BY A XANTHINE OXIDASE-DEPENDENT NEUTROPHIL MECHANISM
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DOI：
10.1006/jsre.1993.1072
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发表时间：
1993-05-01
影响因子：
2.2
通讯作者：
BANERJEE, A
中科院分区：
文献类型：
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作者：
KOIKE, K;MOORE, FA;BANERJEE, A
中性粒细胞(PMN)被认为在创伤后成人呼吸窘迫综合征的发病机制中起关键作用。我们先前已经证明，肠缺血/再灌注(I/R)通过一个需要中性粒细胞的过程产生肺损伤。最近，我们已经证明了黄嘌呤氧化酶(XO)起了一定的作用。本研究的目的是在肠I/R诱导的肺损伤模型中表征XO活性与PMN之间的机制序列。正常大鼠和XO失活大鼠(富钨、缺钼饮食)行肠系膜上动脉阻断45min。再灌流6小时后，取血，取肠、肺组织。用髓过氧化物酶(MPO)定量测定肠道和肺组织中PMN的含量，循环PMN激发时测定有无激活刺激时超氧化物歧化产物的产生，以fMLP.125I标记的白蛋白渗漏作为肺内皮细胞通透性的标志。我们观察到，肠道I/R增加了肠道MPO水平，启动了循环PMN，增加了肺MPO水平，并引发了远端肺渗漏。XO灭活可消除肠道MPO活性，减弱循环中PMN的启动，并阻断肺漏。综上所述，XO在内脏低灌流后远隔器官损伤的发病机制中起重要作用。
Neutrophils (PMNs) are believed to play a key role in the pathogenesis of postinjury adult respiratory distress syndrome. We have previously shown that gut ischemia/reperfusion (I/R) produces lung injury by a process that requires PMNs. More recently, we have shown that xanthine oxidase (XO) plays a role. The purpose of this study was to characterize the mechanistic sequencing of XO activity versus the PMN in this model of gut I/R-induced lung injury. Normal and XO-inactivated (tungsten enriched, molybdenum depleted diet) rats underwent 45 min of superior mesenteric artery occlusion. After 6 hr reperfusion, blood was sampled and gut and lungs harvested. Myeloperoxidase (MPO) was used to quantitate PMN presence in the gut and lungs, while circulating PMN priming was measured as the difference in superoxide production with and without the activating stimulus, fMLP.125I-labeled albumin leak was used as a marker for lung endothelial permeability. We observed that the gut I/R increased gut MPO levels, primed circulating PMNs, increased lung MPO levels, and provoked distant lung leak. XO inactivation abolished gut MPO activity, attenuated circulating PMN priming, and blocked lung leak. In conclusion, XO plays a proximal role in the pathogenesis of remote organ injury following splanchnic hypoperfusion.