Sznajder J I, Olivera W G, Ridge K M, Rutschman D H
Michael Reese Hospital, University of Illinois at Chicago, USA.
Am J Respir Crit Care Med. 1995 May;151(5):1519-25. doi: 10.1164/ajrccm.151.5.7735609.
Sodium transport across the lung epithelium is predominantly effected by apical amiloride-sensitive Na+ channels and basolaterally located ouabain-sensitive Na,K-ATPases. Previously, we reported that subacute hyperoxia caused an increase in active Na+ transport in rat lungs paralleling Na,K-ATPase upregulation in alveolar Type 2 cells isolated from the same lungs. In the present study we set out to quantify the amiloride-sensitive Na+ flux and ouabain-sensitive active Na+ transport in the isolated-perfused, fluid-filled lung model from rats exposed to 85% O2 for 7 d compared with normoxic control rats. We found increased transpulmonary albumin flux and permeability to small solutes (Na+ and mannitol) in hyperoxic rat lungs compared with controls. Amiloride (10(-5) M) instilled into rat airspaces inhibited active Na+ transport by approximately 62% in control rat lungs and by approximately 87% in lungs from rats exposed to hyperoxia, without further changing permeability for Na+ and mannitol. Ouabain (10(-5)M) perfused through the pulmonary circulation decreased active Na+ transport by approximately 40% in normal rat lungs and by approximately 52% in lungs from rats exposed to hyperoxia. We conclude that active Na+ transport and edema clearance are increased in the subacute hyperoxic lung injury in rats, caused in part by the upregulation of amiloride-sensitive apical Na+ channels and alveolar epithelial Na,K-ATPases. Conceivably, the upregulation of alveolar epithelial Na+ channels and Na,K-ATPases protects against the effects of lung injury in this model by contributing to effective edema clearance.
钠跨肺上皮的转运主要通过顶端的氨氯地平敏感的Na⁺通道和基底外侧的哇巴因敏感的Na,K-ATP酶来实现。此前，我们报道过亚急性高氧会导致大鼠肺中主动Na⁺转运增加，这与从同一肺中分离出的肺泡Ⅱ型细胞中Na,K-ATP酶上调相平行。在本研究中，我们着手量化在与常氧对照大鼠相比，暴露于85%氧气7天的大鼠的离体灌注、充满液体的肺模型中氨氯地平敏感的Na⁺通量和哇巴因敏感的主动Na⁺转运。我们发现，与对照组相比，高氧大鼠肺中的经肺白蛋白通量增加，对小溶质（Na⁺和甘露醇）的通透性增加。将氨氯地平（10⁻⁵ M）注入大鼠气腔，在对照大鼠肺中抑制了约62%的主动Na⁺转运，在高氧暴露大鼠的肺中抑制了约87%，而Na⁺和甘露醇的通透性没有进一步改变。通过肺循环灌注哇巴因（10⁻⁵ M），在正常大鼠肺中使主动Na⁺转运降低约40%，在高氧暴露大鼠的肺中降低约52%。我们得出结论，在大鼠亚急性高氧肺损伤中，主动Na⁺转运和水肿清除增加，部分原因是氨氯地平敏感的顶端Na⁺通道和肺泡上皮Na,K-ATP酶上调。可以想象，在该模型中，肺泡上皮Na⁺通道和Na,K-ATP酶的上调通过促进有效的水肿清除来保护肺免受损伤的影响。
