ROLE OF TUMOR NECROSIS FACTOR-ALPHA IN THE PATHOPHYSIOLOGIC ALTERATIONS AFTER HEPATIC ISCHEMIA REPERFUSION INJURY IN THE RAT
ROLE OF TUMOR NECROSIS FACTOR-ALPHA IN THE PATHOPHYSIOLOGIC ALTERATIONS AFTER HEPATIC ISCHEMIA REPERFUSION INJURY IN THE RAT
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DOI：
10.1172/jci114656
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发表时间：
1990-06-01
影响因子：
15.9
通讯作者：
CAMPBELL, DA
中科院分区：
文献类型：
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作者：
COLLETTI, LM;REMICK, DG;CAMPBELL, DA
细胞因子被认为是器官损伤的关键早期介质。我们试图确定严重的肝缺血/再灌注损伤是否导致肿瘤坏死因子-α。（TNF-α）释放，随后局部和全身组织损伤。肝叶缺血90分钟后，在所有14只实验动物的血浆中，在再灌注期间可测量到TNF，水平峰值在9和352 pg/ml之间。在这些动物的血浆中未检出内毒素。 肺损伤，表现为肝再灌注后出现嗜酸性细胞浸润、水肿和肺泡内出血。使用髓过氧化物酶（MPO）测定定量嗜中性粒细胞浸润;这表明仅再灌注1小时后MPO显著增加。抗TNF抗血清预处理可显著降低肝脏再灌注后肺组织MPO活性。再灌注12小时后，有肺泡内出血和肺水肿的组织学证据。形态学评估表明，预处理与抗TNF抗血清能够完全抑制肺水肿的发展。血清谷氨酰胺转氨酶（ALT）在3 h和24 h出现峰值，以定量肝损伤程度。抗TNF抗血清预处理能够显著降低这两个峰值升高。这些数据表明，肝缺血/再灌注导致TNF的产生，并且这种TNF与肺和肝损伤密切相关。
Cytokines are recognized as critical early mediators of organ injury. We attempted to determine whether or not severe hepatic ischemia/reperfusion injury results in tumor necrosis factor-.alpha. (TNF-.alpha.) release with subsequent local and systemic tissue injury. After 90 min of lobar hepatic ischemia, TNF was measurable during the reperfusion period in the plasma of all 14 experimental animals, with levels peaking between 9 and 352 pg/ml. Endotoxin was undetectable in the plasma of these animals. Pulmonary injury, as evidenced by a neutrophilic infiltrate, edema and intra-alveolar hemorrhage developed after hepatic reperfusion. The neutrophilic infiltrate was quantitated using a myeloperoxidase (MPO) assay; this demonstrated a significant increase in MPO after only 1 h of reperfusion. Anti-TNF antiserum pretreatment significantly reduced the pulmonary MPO after hepatic reperfusion. After a 12-h reperfusion period, there was histologic evidence of intra-alveolar hemorrhage and pulmonary edema. Morphometric assessment showed that pretreatment with anti-TNF antiserum was able to completely inhibit the development of pulmonary edema. Liver injury was quantitatived by measuring serum glutamic pyruvic transaminase which showed peaks at 3 and 24 h. Anti-TNF antiserum pretreatment was able to significantly reduced both of these peak elevations. These data show that hepatic ischemia/reperfusion results in TNF production, and that this TNF is intimately associated with pulmonary and hepatic injury.