Ulinastatin Improves Pulmonary Function in Severe Burn-Induced Acute Lung Injury by Attenuating Inflammatory Response
Ulinastatin Improves Pulmonary Function in Severe Burn-Induced Acute Lung Injury by Attenuating Inflammatory Response
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DOI：
10.1097/ta.0b013e3182127d48
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Yao, Min
中科院分区：
文献类型：
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作者：
Fang, Yong;Xu, Peng;Yao, Min
背景：严重皮肤烧伤后的急性全身炎症反应可介导烧伤引起的急性肺损伤。乌司他丁可能是一种有效的干预措施，因为它可以减轻内毒素引起的全身炎症反应，改善缺血休克和再灌注时的心肌功能。方法：大鼠烧伤创面厚度达到体表面积的30%，进行延迟复苏。治疗组给予乌司他丁5万U/kg，烧伤组只给予载药。另一组没有烧伤，但治疗方法相同。杀死后，采集血液和肺样本用于组织学和炎症介质的测量。结果：乌司他丁显著降低烧伤大鼠局部和全身肿瘤坏死因子- α、白细胞介素-1 β、-6和-8 mRNA和蛋白水平。乌司他丁可抑制肺内中性粒细胞弹性酶和髓过氧化物酶的分泌及肺上皮表面细胞间粘附分子-1的表达。乌司他丁也降低了肺微血管通透性的增加。与这些发现一致，乌司他丁改善了烧伤大鼠的肺水肿和肺氧合。结论：这些结果表明，乌司他丁对炎症介质产生、中性粒细胞活化和微血管通透性的抑制作用与严重烧伤引起的急性肺损伤肺功能的恢复有关，并提示乌司他丁可能作为危重烧伤护理的潜在治疗药物。
Background: Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion.Methods: Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators.Results: Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1 beta, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats.Conclusions: These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care.