Finley N, Norlin A, Baines D L, Folkesson H G
Department of Animal Physiology, Lund University, S-223 62 Lund, Sweden.
J Clin Invest. 1998 Mar 1;101(5):972-81. doi: 10.1172/JCI1478.
Transition from placental to pulmonary oxygenation at birth depends on a rapid removal of fetal lung fluid from the developing alveoli. Alveolar fluid clearance was examined in ventilated, anesthetized developing guinea pigs of the ages newborn, 2-d-old, 5-d-old, 30-d-old, and 60-d-old (adult). An isosmolar 5% albumin solution was instilled into the lungs of the guinea pigs; the guinea pigs were then studied for 1 h. Alveolar fluid clearance was measured from the increase in alveolar protein concentration as water was reabsorbed. Newborn guinea pigs had a very high alveolar fluid clearance rate that declined rapidly within the first 5 postnatal days towards adult levels. The high alveolar fluid clearance at birth was apparently mediated by the beta-adrenergic system as demonstrated by the elevated plasma epinephrine levels and the increased sensitivity to inhibition by the beta-adrenergic antagonist propranolol immediately after birth. Surprisingly, exogenous addition of epinephrine was not able to stimulate alveolar fluid clearance in the newborn lung, but exogenous epinephrine stimulation increased over time to adult levels. The elevated alveolar fluid clearance at birth was associated with a significantly greater amiloride sensitivity in the newborn guinea pig lung. Northern blot analysis of distal lung tissue as well as isolated alveolar epithelial type II cells showed and confirmed higher levels of the alpha-subunit of the epithelial sodium channel mRNA in the newborn lung that rapidly tapered off toward adult levels. In conclusion, these data demonstrate the importance of the beta-adrenergic system and amiloride-sensitive sodium transporting pathways for clearance of fetal lung fluid at birth.
出生时从胎盘氧合向肺氧合的转变取决于快速清除发育中肺泡内的胎儿肺液。在通气、麻醉的新生、2日龄、5日龄、30日龄和60日龄(成年)发育中的豚鼠中检测肺泡液清除情况。将等渗5%白蛋白溶液注入豚鼠肺内;然后对豚鼠进行1小时的研究。通过水重吸收时肺泡蛋白浓度的增加来测量肺泡液清除情况。新生豚鼠的肺泡液清除率非常高,在出生后的头5天内迅速下降至成年水平。出生时高肺泡液清除率显然由β-肾上腺素能系统介导,这可通过出生后立即升高的血浆肾上腺素水平以及对β-肾上腺素能拮抗剂普萘洛尔抑制作用的敏感性增加来证明。令人惊讶的是,外源性添加肾上腺素并不能刺激新生肺的肺泡液清除,但外源性肾上腺素刺激随时间增加至成年水平。出生时升高的肺泡液清除率与新生豚鼠肺对氨氯吡咪的敏感性显著更高有关。对远端肺组织以及分离的肺泡Ⅱ型上皮细胞进行的Northern印迹分析显示并证实,新生肺中上皮钠通道mRNA的α亚基水平较高,且迅速向成年水平逐渐降低。总之,这些数据证明了β-肾上腺素能系统和氨氯吡咪敏感的钠转运途径在出生时清除胎儿肺液中的重要性。