THE PRODUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND THE DEVELOPMENT OF A PULMONARY CAPILLARY INJURY FOLLOWING HEPATIC ISCHEMIA REPERFUSION
THE PRODUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND THE DEVELOPMENT OF A PULMONARY CAPILLARY INJURY FOLLOWING HEPATIC ISCHEMIA REPERFUSION
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DOI：
10.1097/00007890-199002000-00008
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发表时间：
1990-02-01
期刊：
影响因子：
6.2
通讯作者：
CAMPBELL, DA
中科院分区：
文献类型：
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作者：
COLLETTI, LM;BURTCH, GD;CAMPBELL, DA
肝脏中大量固定的巨噬细胞使其成为细胞因子的潜在丰富来源。我们以前已经证明，一个孤立的和严重的缺血/再灌注损伤的肝脏细胞因子的释放，特别是肿瘤坏死因子α，TNF参与肺病理的发展。本研究的目的是确定不同时间的肝缺血后TNF释放的动力学，并进一步研究随后的急性肺损伤。在连续的时间点获得肝上的血液样品后，45-，60-，75-，或90分钟的缺血性损伤的一段大鼠肝脏，随后再灌注。使用基于WEHI 164细胞系的生物测定法，测量所有实验动物的血浆TNF水平;假手术对照动物的水平不可检测。然后使用标准的125 I标记的白蛋白洗脱技术测量肺毛细血管通透性的变化，随后再灌注90分钟的缺血性损伤。在肝脏再灌注后9至12小时观察到平均渗透指数显著增加（. 601+/-。102与之相比114+/-。085，P< 0.005）。在诱导肝缺血之前用抗TNF抗血清处理的动物与用无TNF阻断特性的兔血清预处理的动物相比，肺毛细血管渗漏显著减少（. 184+/-。029对。694+/-。052，P< 0.005）。TNF释放遵循中度和重度缺血性损伤的肝脏和结果牵连TNF作为一个重要的介质增加肺毛细血管通透性。这些实验证实了先前的组织学研究，其证明了肝缺血/再灌注后的肺水肿和肺泡内出血，随后通过用抗TNF抗血清预处理阻断组织学损伤。
The large mass of fixed macrophages resident in the liver make it a potentially rich source of cytokines. We have previously demonstrated that an isolated and severe ischemia/reperfusion injury to the liver results in cytokine release, specifically tumor necrosis factor alpha, and that TNF is then involved in the development of pulmonary pathology. This study was designed to determine the kinetics of TNF release following varying periods of hepatic ischemia and to further investigate the acute lung injury that follows. Suprahepatic blood samples were obtained at serial time points following a 45-, 60-, 75-, or 90-min ischemic insult to a segment of the rat liver with subsequent reperfusion. Using a bioassay based on the WEHI 164 cell line, plasma TNF levels were measured in all experimental animals; sham-operated control animals had undetectable levels. Changes in pulmonary capillary permeability were then measured using a standard 125I-labeled albumin washout technique following a 90-min ischemic insult with subsequent reperfusion. A significant increase in the mean permeability index was observed 9 to 12 hr following hepatic reperfusion (. 601+/-. 102 as compared with. 114+/-. 085 in sham-operated controls, P< 0.005). Animals treated with anti-TNF antiserum prior to the induction of hepatic ischemia had a significantly reduced pulmonary capillary leak compared to animals pretreated with rabbit serum without TNF-blocking properties (. 184+/-. 029 versus. 694+/-. 052 for the control serum, P< 0.005). TNF release follows both moderate and severe ischemic injury to the liver and the results reported here implicate TNF as an important mediator of increased pulmonary capillary permeability. These experiments confirm previous histologic studies that demonstrated pulmonary edema and intra-alveolar hemorrhage following hepatic ischemia/reperfusion, with subsequent blockade of the histologic injury by pretreatment with anti-TNF antiserum.