烧伤复合内毒素血症早期肺损害及其机制的实验研究

目的：探讨烧伤复合内毒素血症早期肺损害的病变特点及发生机制。方法：采用20％Ⅲ度体表烧伤复合一次性腹腔内注射低剂量内毒素（1mg/kg)为实验动物模型并分别以单纯烧伤（单烧组）、单纯内毒素注射（单注组）、生理盐水为对照组，血小板激活因子（PAF）受体拮抗剂BN50739为治疗组。动态观察烧伤后0．5、1、1．5、3、6、12、24和48小时肺的形态和功能变化，血浆肿瘤坏死因子（TNF）、PAF、肺泡灌洗液（BALF）中蛋白含量以及肺组织内TNF分布。结果：烧注组出现肺病变较单烧组、单注组出现早，程度重，持续时间长；病变发展过程可大致分为间质性肺水肿、间质性肺炎和肺泡内渗出3个阶段。烧注组血PAF和TNF分别于伤后0．5和1小时显著高于对照组，于1．5小时呈大峰值并持续至伤后48小时；BALF蛋白含量也于伤后0．5小时明显升高；治疗组血PAF、TNF和BALF蛋白含量均显著下降，TNF阳性细胞也明显减少，肺水肿以及损伤程度明显减轻。结论：PAF和TNF是烧伤内毒素血症急性肺损伤时的重要炎症介质，能增加肺血管对蛋白质的通透性，能相互促进合成，发挥协同损伤效应。而PAF拮抗剂BN50739能阻断这些效应，减轻肺损伤。

The early pathological changes and pathogenesis of acute lung injury in rats after burns combined with endotoxemia

Objective:To study the pathogenesis of acute lung injury following burns combined with endotoxemia.Methods:The rats subjected to 20% total body surface area (TBSA) fullthickness thermal injury,followed by intraperitoneal endotoxin challenge (1 mg/kg B.W.E.coli O111B4,Sigma).The histological and ultrastructural changes of lungs,plateletactivating factor (PAF) and tumor necrosis factor (TNF) levels in plasma,protein content in bronchoalveolar lavage fluid (BALF) were dynamically determined at 0 5,1,1 5,3,6,12,24 and 48 hours after burn injury or endotoxin injection.Results:A series of early morphological changes of lungs could be found after burn injury combined with endotoxemia (BE).The course of the pathological changes might be divided into the following three phases:interstitial pulmonary edema,interstitial pneumonia and alveolar effusion.The plasma levels of PAF and TNF in BE group significantly increased at 0 5 and 1 hour postburn and peaked at 1 5 hours,kept high values up to 48 hours.The protein contents in BALF in BE group markedly increased from 0 5 to 1 hour after injury.Pretreatment with BN50739,however,could significantly reduce the plasma levels of PAF and TNF and the protein content in BALF,and the severity of lung injury was also attenuated.Conclusion:PAF and TNF are early inflammatory mediators during burns combined with endotoxin injection,and the interaction of PAF and TNF might play a key role in the pathogenesis of early acute lung injury.Pretreatment with BN50739 could markedly inhibit the pulmonary inflammatory response and attenuate the acute lung injury following burns combined with endotoxemia.