West J B, Mathieu-Costello O
Department of Medicine, University of California at San Diego, La Jolla 92093-0623, USA.
Annu Rev Physiol. 1999;61:543-72. doi: 10.1146/annurev.physiol.61.1.543.
The pulmonary blood-gas barrier needs to satisfy two conflicting requirements. It must be extremely thin for efficient gas exchange, but also immensely strong to withstand the extremely high stresses in the capillary wall when capillary pressure rises during exercise. The strength of the blood-gas barrier on the thin side is attributable to the type IV collagen in the basement membranes. However, when the wall stresses rise to very high levels, ultrastructural changes in the barrier occur, a condition known as stress failure. Physiological conditions that alter the properties of the barrier include intense exercise in elite human athletes. Some animals, such as Thoroughbred racehorses, consistently break their alveolar capillaries during galloping, causing hemorrhage. Pathophysiological conditions causing stress failure include neurogenic pulmonary edema, high-altitude pulmonary edema, left heart failure, and overinflation of the lung. Remodeling of the capillary wall occurs in response to increased wall stress, a good example being the thickening of the capillary basement membrane in diseases such as mitral stenosis. The blood-gas barrier is able to maintain its extreme thinness with sufficient strength only through continual regulation of its wall structure. Recent experimental work suggests that rapid changes in gene expression for extracellular matrix proteins and growth factors occur in response to increases in capillary wall stress. How the blood-gas barrier is regulated to be extremely thin but sufficiently strong is a central issue in lung biology.
肺气血屏障需要满足两个相互矛盾的要求。它必须极其薄以实现高效的气体交换，但又必须非常坚固，以承受运动期间毛细血管压力升高时毛细血管壁中极高的压力。气血屏障薄侧的强度归因于基底膜中的IV型胶原蛋白。然而，当壁应力上升到非常高的水平时，屏障会发生超微结构变化，这种情况称为应力衰竭。改变屏障特性的生理状况包括精英人类运动员的剧烈运动。一些动物，如纯种赛马，在奔跑时会持续破裂肺泡毛细血管，导致出血。导致应力衰竭的病理生理状况包括神经源性肺水肿、高原肺水肿、左心衰竭和肺过度膨胀。毛细血管壁的重塑是对壁应力增加的反应，一个很好的例子是二尖瓣狭窄等疾病中毛细血管基底膜的增厚。气血屏障只有通过不断调节其壁结构，才能保持其极薄的厚度并具有足够的强度。最近的实验工作表明，细胞外基质蛋白和生长因子的基因表达会随着毛细血管壁应力的增加而迅速变化。如何将气血屏障调节得极其薄但又足够坚固是肺生物学中的一个核心问题。
