EVIDENCE FOR TUMOR NECROSIS FACTOR-INDUCED PULMONARY MICROVASCULAR INJURY AFTER INTESTINAL ISCHEMIA REPERFUSION INJURY
EVIDENCE FOR TUMOR NECROSIS FACTOR-INDUCED PULMONARY MICROVASCULAR INJURY AFTER INTESTINAL ISCHEMIA REPERFUSION INJURY
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DOI：
10.1097/00000658-199012000-00007
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发表时间：
1990-12-01
影响因子：
9
通讯作者：
KUNKEL, SI
中科院分区：
文献类型：
--
作者：
CATY, MG;GUICE, KS;KUNKEL, SI
以微血管通透性增加为特征的急性肺损伤是多器官系统衰竭和成人呼吸窘迫综合征的一个特征。肠缺血再灌注损伤与这种类型的急性肺损伤有关。这些实验的目的是检查连接这两个过程的致病介质，特别强调内毒素和肿瘤坏死因子。α的作用。(TNF.alpha)。先前描述的这种肠缺血再灌注大鼠模型的急性肺损伤特征包括肺中性粒细胞隔离、肺组织ATP耗竭、肺泡内皮细胞破坏和微血管通透性增加。假手术动物和肠道缺血性损伤持续时间小于60分钟的动物的体循环血浆TNF水平非常低或检测不到。肠缺血120分钟，TNF升高至1.19 +-。0.50 \毫升。再灌注15和30分钟可使循环TNF水平增加5- 10倍(6.61 .+-。3.11 U/mL, p < 0.05, p < 10.41 +-。5.41 U/mL, p = 0.004)；然而，这种循环TNF的增加是短暂的，并在开始再灌注后60分钟内大部分清除。门静脉内毒素水平在全身性血浆中TNF出现之前显著升高，提示肠源性内毒素可能诱导肝巨噬细胞释放TNF进入体循环。抗肿瘤坏死因子抗体减弱了该制剂中肺微血管通透性的增加，但没有阻止肺中性粒细胞的隔离。这些观察结果表明，内毒素和TNF在这种急性肺损伤中具有致病作用，但中性粒细胞粘附内皮细胞的机制可能独立于TNF。中性粒细胞在肺内的积累，但在TNF抗体的存在下防止血管通透性增加，这可能意味着TNF在中性粒细胞活化过程中的体内作用。这些研究提供了更多的证据，证明内源性炎症介质在局部组织损伤引起全身性损伤发展中的重要性。
Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on roles of endotoxin and tumor necrosis factor .alpha. (TNF.alpha.). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 .+-. 0.50 \mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 .+-. 3.11 U/mL, p > 0.05 and 10.41 .+-. 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury.