CHANGES IN SUBPHASE AGGREGATES IN RABBITS INJURED BY FREE FATTY-ACID
CHANGES IN SUBPHASE AGGREGATES IN RABBITS INJURED BY FREE FATTY-ACID
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DOI：
10.1164/ajrccm.149.5.8173747
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发表时间：
1994-05-01
影响因子：
24.7
通讯作者：
NOTTER, RH
中科院分区：
文献类型：
--
作者：
HALL, SB;HYDE, RW;NOTTER, RH
用静脉内游离脂肪酸处理的兔遭受急性肺损伤。尽管表面活性剂磷脂水平正常，但通过支气管肺泡灌洗（BAL）从这些肺中获得的材料在体外降低表面张力的能力显著受损。虽然大量的表面活性抑制剂存在于BAL中，但它们的作用不足以解释表面活性剂失活的程度。本研究确定表面活性剂聚集体的改变是否可以解释脂肪酸肺损伤中表面活性剂功能的丧失。在受伤的动物中，发现通过离心造粒回收的较大的、最活跃的表面活性剂颗粒的量减少。与对照聚集体相比，剩余的大颗粒具有降低的表面活性。此外，受伤动物中的大颗粒在平衡离心后的蔗糖梯度上的密度高于对照动物。与损伤BAL中存在的血清组分的相互作用可以解释这些较高的密度。通过补充正常水平的来自受损肺的颗粒，受损BAL降低表面张力的能力得到改善。用对照大聚集体补充受损的BAL进一步改善了活性，并恢复了将表面张力降低至< 1 mN/m的能力。因此，受伤动物中大的表面活性剂聚集体的量和活性的降低显著促进了所观察到的表面活性剂的失活。表面活性剂聚集体改变导致表面活性剂功能下降是其他形式急性肺损伤的常见机制，在损伤肺中使用外源性表面活性剂的治疗设计需要考虑使表面活性剂功能恢复正常的策略。
Rabbits treated with intravenous free fatty acid suffer an acute lung injury. Material obtained from these lungs by bronchoalveolar lavage (BAL) has dramatically impaired ability to lower surface tension in vitro despite normal levels of surfactant phospholipids. Although large quantities of surface-active inhibitors are present in BAL, their effects are not sufficient to explain the magnitude of surfactant inactivation. This study determines if alterations in the surfactant aggregates can explain the loss of surfactant function in fatty acid lung injury. In injured animals, the larger, most active surfactant particles recovered by centrifugal pelleting were found to be decreased in amount. The remaining large particles had reduced surface activity compared with control aggregates. In addition, large particles in injured animals had a higher density than control animals on sucrose gradients following equilibrium centrifugation. Interaction with serum components present in the injured BAL could explain these higher densities. The ability of the injured BAL to lower surface tension was improved by supplementation with normal levels of particles from injured lungs. Supplementation of injured BAL with control large aggregates improved activity further and restored the ability to lower surface tension to < 1 mN/m. Therefore both the decreased amount and activity of large surfactant aggregates in injured animals contributed significantly to the observed inactivation of surfactant. Diminished surfactant function from alteration in surfactant aggregates is a mechanism common to other forms of acute lung injury, and the design of therapies with exogenous surfactants in injured lungs will need to consider strategies that restore surfactant function towards normal.