O'Brodovich H M
MRC Group in Lung Development, Hospital for Sick Children, Toronto, Ontario, Canada.
Proc Assoc Am Physicians. 1996 Sep;108(5):345-55.
Noninfective acute respiratory disease develops in approximately 1% of all newborn infants and results in their admission to a critical care unit. Transient tachypnea of the newborn occurs as a result of a delay in the clearance of fetal lung liquid; however, respiratory distress syndrome, typically thought to be exclusively a problem of relative surfactant deficiency, is now suspected to be characterized by an even greater air space fluid burden from the inability to absorb fetal lung liquid. In vivo experiments have demonstrated that the lung epithelium secretes Cl and fluid throughout gestation and develops the ability to actively reabsorb Na+ only during late gestation. At birth, the mature lung switches from active Cl- (fluid) secretion to active Na+ (fluid) absorption in response to circulating catecholamines. Changes in oxygen tension augment the Na(+)-transporting capacity of the epithelium and increase gene expression for the epithelial Na+ channel (ENaC). The inability of the immature fetal lung to switch from fluid secretion to fluid absorption results, at least in large part, from an immaturity in the expression of ENaC, which can be upregulated by glucocorticosteroids. Both pharmacological blockade of the lung's epithelial Na+ channel and genetic knockout experiments using mice deficient in the ENaC pore-forming subunit have demonstrated the critical physiological importance of lung Na+ transport at birth. When Na+ transport is ineffective, newborn animals develop respiratory distress and hypoxemia, retain their fetal lung liquid and, in the case of the ENaC knockout mice, die. Bioelectrical studies of human infants' nasal epithelia demonstrate that both transient tachypnea of the newborn and respiratory distress syndrome have defective amiloride-sensitive Na+ transport. These results suggest that neonatal respiratory distress syndrome has, in addition to a relative deficiency in surfactant, defective Na+ transport, which plays a mechanistic role in the development of the disease.
约1%的新生儿会发生非感染性急性呼吸道疾病，并因此入住重症监护病房。新生儿暂时性呼吸急促是由于胎儿肺液清除延迟所致；然而，呼吸窘迫综合征通常被认为完全是相对表面活性物质缺乏的问题，现在怀疑其特征是由于无法吸收胎儿肺液而导致气腔液体负担更大。体内实验表明，肺上皮在整个妊娠期都分泌氯离子和液体，并且仅在妊娠晚期才发展出主动重吸收钠离子的能力。出生时，成熟的肺会因循环儿茶酚胺的作用而从主动分泌氯离子（液体）转变为主动吸收钠离子（液体）。氧张力的变化增强了上皮细胞的钠离子转运能力，并增加了上皮钠离子通道（ENaC）的基因表达。未成熟的胎儿肺无法从液体分泌转变为液体吸收，至少在很大程度上是由于ENaC表达不成熟所致，而糖皮质激素可上调ENaC的表达。对肺上皮钠离子通道的药理学阻断以及使用缺乏ENaC孔形成亚基的小鼠进行的基因敲除实验均证明了出生时肺钠离子转运的关键生理重要性。当钠离子转运无效时，新生动物会出现呼吸窘迫和低氧血症，保留胎儿肺液，而对于ENaC基因敲除小鼠，则会死亡。对人类婴儿鼻上皮的生物电研究表明，新生儿暂时性呼吸急促和呼吸窘迫综合征都存在对氨氯地平敏感的钠离子转运缺陷。这些结果表明，除了表面活性物质相对缺乏外，新生儿呼吸窘迫综合征还存在钠离子转运缺陷，这在该疾病的发生机制中起作用。
