Ikegami Machiko, Weaver Timothy E, Grant Shawn N, Whitsett Jeffrey A
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Am J Respir Cell Mol Biol. 2009 Oct;41(4):433-9. doi: 10.1165/rcmb.2008-0359OC. Epub 2009 Feb 6.
Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb(-/-) mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after depletion of Sftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2 days of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2-mum-diameter microbeads through jugular vein were retained within narrowed pulmonary capillaries after reduction of SP-B. Ultrastructure studies demonstrated that the capillary protrusion typical of the normal alveolar-capillary unit was reduced in size, consistent with altered pulmonary blood flow. Pulmonary hypertension and intrapulmonary shunting are commonly associated with surfactant deficiency and dysfunction in neonates and adults with respiratory distress syndromes. Increased surfactant surface tension caused by reduction in SP-B induced narrowing of alveolar capillaries and oxygen desaturation, demonstrating an important role of surface tension-lowering properties of surfactant in the regulation of pulmonary vascular perfusion.
肺泡毛细血管位于肺泡上皮附近且在表面活性物质层之下。我们推测肺泡毛细血管的形态及伴随的氧合作用受肺泡表面活性物质表面张力的影响。为证实我们的推测,通过在Sftpb(-/-)小鼠中条件性表达表面活性物质蛋白(SP)-B来调节表面活性物质表面张力,从而在Sftpb耗竭后24小时内抑制体内表面活性物质降低表面张力的特性。在SP-B缺乏2天后,分离出的表面活性物质的最小表面张力增加,氧饱和度显著降低,同时伴有肺泡毛细血管变形。降低SP-B后,经颈静脉血管内注射的直径3.2微米的微珠滞留在变窄的肺毛细血管内。超微结构研究表明,正常肺泡-毛细血管单元典型的毛细血管突出部分尺寸减小,这与肺血流改变一致。在患有呼吸窘迫综合征的新生儿和成人中,肺动脉高压和肺内分流通常与表面活性物质缺乏和功能障碍有关。SP-B减少导致表面活性物质表面张力增加,进而引起肺泡毛细血管变窄和氧饱和度降低,这表明表面活性物质降低表面张力的特性在调节肺血管灌注中起重要作用。