Brigham K L
Prog Biochem Pharmacol. 1985;20:26-37.
Gram-negative endotoxemia in chronically instrumented sheep causes diffuse lung inflammation. Pathophysiologic responses of the lung include marked changes in lung mechanics, pulmonary vasoconstriction, increased lung vascular permeability, and capillary endothelial injury. Over the course of the response to endotoxemia, cyclooxygenase and lipoxygenase products of arachidonic acid are released into lung lymph and the time course of the two classes of compounds is different. Thromboxane concentrations in lung lymph increase early, coincident with the most marked changes in lung mechanics and the most severe pulmonary hypertension. Concentrations of a prostacyclin metabolite also increase during this early phase of the endotoxin response but peak levels in lung lymph appear slightly later than that for thromboxane. Concentrations of these cyclooxygenase products subside as the later phase of increased vascular permeability develops. Lung lymph concentrations of two lipoxygenase products, 5- and 12-HETE, increase late in the endotoxin reaction, approximately coincident with physiologic evidence of increased lung vascular permeability. Neutrophil chemotactic activity appears in lung lymph early after endotoxin infusion and persists for several hours. Drugs which inhibit cyclooxygenase attenuate the early changes in lung mechanics and the early pulmonary hypertension after endotoxemia, but do not prevent the late phase increase in vascular permeability, suggesting that the net effect of endogenous generation of cyclooxygenase products explains the early constrictor phase of the reaction, but not the later capillary injury. However, neutrophil depletion prevents the early changes in lung mechanics without preventing the coincident pulmonary hypertension or the increase in lung lymph thromboxane concentrations which may indicate that the cell source of constrictor cyclooxygenase products mediating changes in lung mechanics is different than that for products causing pulmonary vasoconstriction. The specific role of prostacyclin in the lungs' response to endotoxemia is not clear. The temporal course of prostacyclin release suggests that it may play a role in moderating the pulmonary hypertension and changes in lung mechanics. The fact that neutrophil depletion, corticosteroids, and the antioxidant n-acetylcysteine diminish both the endotoxin-induced increase in lung vascular permeability and lung prostacyclin release may indicate that the release of prostacyclin is a response to endothelial injury.(ABSTRACT TRUNCATED AT 400 WORDS)
长期植入仪器的绵羊发生革兰氏阴性菌血症会导致弥漫性肺部炎症。肺部的病理生理反应包括肺力学的显著变化、肺血管收缩、肺血管通透性增加以及毛细血管内皮损伤。在内毒素血症反应过程中，花生四烯酸的环氧化酶和脂氧化酶产物会释放到肺淋巴中，这两类化合物的时间进程不同。肺淋巴中的血栓素浓度早期升高，与肺力学最显著变化和最严重的肺动脉高压同时出现。前列环素代谢物的浓度在内毒素反应的早期阶段也会升高，但肺淋巴中的峰值水平出现时间略晚于血栓素。随着血管通透性增加的后期阶段发展，这些环氧化酶产物的浓度会下降。两种脂氧化酶产物5-和12-羟基二十碳四烯酸（HETE）的肺淋巴浓度在内毒素反应后期升高，大约与肺血管通透性增加的生理证据同时出现。内毒素注入后早期肺淋巴中出现中性粒细胞趋化活性，并持续数小时。抑制环氧化酶的药物可减轻内毒素血症后肺力学的早期变化和早期肺动脉高压，但不能阻止后期血管通透性的增加，这表明内源性环氧化酶产物的净效应解释了反应的早期收缩期，但不能解释后期的毛细血管损伤。然而，中性粒细胞耗竭可防止肺力学的早期变化，却不能防止同时出现的肺动脉高压或肺淋巴血栓素浓度的增加，这可能表明介导肺力学变化的收缩性环氧化酶产物的细胞来源与引起肺血管收缩的产物不同。前列环素在肺部对内毒素血症反应中的具体作用尚不清楚。前列环素释放的时间进程表明它可能在减轻肺动脉高压和肺力学变化中起作用。中性粒细胞耗竭、皮质类固醇和抗氧化剂N-乙酰半胱氨酸既能减少内毒素诱导的肺血管通透性增加，又能减少肺前列环素释放，这一事实可能表明前列环素的释放是对内皮损伤的一种反应。（摘要截短至400字）
