Biochemical Development of Surface Activity in Mammalian Lung. IV. Pulmonary Lecithin Synthesis in the Human Fetus and Newborn and Etiology of the Respiratory Distress Syndrome
Biochemical Development of Surface Activity in Mammalian Lung. IV. Pulmonary Lecithin Synthesis in the Human Fetus and Newborn and Etiology of the Respiratory Distress Syndrome
复制标题
哺乳动物肺表面活性的生化发展。
作者：
L. Gluck;Marie V Kulovigh;A. Eidelman;L. Cordero;Aida F Khazing
提取物：正常肺中的表面活性复合物衬里肺泡可降低呼气时的表面张力，从而防止肺泡塌陷。表面活动遵循发育时间表。患有特发性呼吸窘迫综合征 (RDS) 的婴儿几乎都是早产，他们的肺部缺乏足够的表面活性，并且缺乏主要表面活性成分卵磷脂。这种缺陷意味着 RDS 是一种“发育疾病”，胎儿和新生儿的卵磷脂合成有时间表。通过检查肺流出物（咽抽吸物、粘液）中的磷脂来研究活人婴儿肺卵磷脂的生物合成，肺流出物中的磷脂与肺灌洗液（肺泡洗液）中的磷脂相同。对分离的卵磷脂和磷脂酰二甲基乙醇胺 (PDME) 的脂肪酸酯进行了检查。 β-碳脂肪酸是卵磷脂合成主要途径的指标：(1) 棕榈酸占优势，表示胞苷二磷酸胆碱 (CDP-胆碱) + D-α,β-甘油二酯 → 卵磷脂（胆碱掺入途径）；(2) 肉豆蔻酸占优势，表示磷脂酰乙醇胺 (PE) + 2 CH3 → PDME + CH3 →卵磷脂（甲基化途径）。18周和20周的胎肺显示CDP-胆碱途径有轻微掺入，不存在PDME，几乎没有甲基化。唾液卵磷脂的脂肪酸与抽吸物中的卵磷脂完全不同。早在妊娠 22-24 周时，就在抽吸物中发现了磷脂酰二甲基乙醇胺 (PDME)（因此甲基化）。早产儿出生后或无 RDS 的抽吸物中的卵磷脂脂肪酸酯与 PDME 脂肪酸非常相似。随着 RDS，PDME 消失，β-碳棕榈酸（因此二棕榈酰卵磷脂）增加。随着康复，PDME 会重新出现，早产儿的主要卵磷脂棕榈酰肉豆蔻酰也会出现。足月婴儿出生时含有更多的 β-碳棕榈酸 (20-40%)，到 12-18 小时时，棕榈酸和肉豆蔻酸的含量相等，这表明两种卵磷脂合成途径都有功能。压力（缺氧酸中毒、体温过低）导致PDME消失和β-碳肉豆蔻酸损失。未患 RDS 的足月婴儿也出现类似变化，这是由于 GDP-胆碱途径合成了足够的卵磷脂。人类胎儿和新生儿的肺部通过甲基化合成卵磷脂的能力使人类能够早产；兔子和羊缺乏这种能力，不会早产，但如果出生太早，就会因呼吸功能不全而死亡。推测：通过在抽吸物（肺排出物）中寻找PDME可以客观地做出RDS的诊断。还可以根据 PDME 的存在与否来确定预后。各种疗法的效果也可以通过这种方式进行评估。本文描述的技术和考虑可用于生化研究其他应激对肺的影响，包括氧毒性和麻醉。
Extract: The surface-active complex lining alveoli in normal lung lowers surface tension on expiration, thus preventing alveolar collapse. Surface activity follows a developmental timetable. Infants with idiopathic respiratory distress syndrome (RDS) almost exclusively are prematurely born, and their lungs lack adequate surface activity and are deficient in the principal surface-active component, lecithin. This deficiency implies that RDS is a “disease of development,” with fetal and neonatal timetables for lecithin synthesis. The biosynthesis of lung lecithin in the living human infant was studied by examining phospholipids in lung effluent (pharyngeal aspirates, mucus), which have identical phospholipids to those in lung lavage (alveolar wash). The fatty acid esters of isolated lecithin and phosphatidyl dimethylethanolamine (PDME) were examined. The β-carbon fatty acids are indicators of the primary pathways of synthesis of lecithin: (1) a preponderance of palmitic acid signifying cytidine diphosphate choline (CDP-choline) + D-α,β-diglyceride → lecithin (choline incorporation pathway) and (2) a preponderance of myristic acid signifying phosphatidyl ethanolamine (PE) + 2 CH3 → PDME + CH3 → lecithin (methylation pathway).Fetal lung of 18 and 20 weeks showed slight incorporation by CDP-choline pathway, absence of PDME, and almost no methylation. Salivary lecithin had totally different fatty acids from lecithin in aspirates. Phosphatidyl dimethylethanolamine (PDME) (therefore methylation) was identified in aspirates as early as 22–24 week-gestation. Lecithin fatty acid esters in aspirates from premature infants after birth or those with no RDS closely resembled PDME fatty acids. With RDS, PDME disappears and β-carbon palmitic acid (therefore dipalmitoyl lecithin) increases. With recovery, PDME reappears, as does the premature infant's major lecithin, palmitoylmyristoyl. Full term infants are born with more β-carbon palmitic acid (20–40%) and by 12–18 hr have equal palmitic and myristic acids, indicating function of both lecithin synthesis pathways. Stress (hypoxia acidosis, hypothermia) cause disappearance of PDME and loss of β-carbon myristic acid. Similar changes in full term infants who do not get RDS are due to adequate lecithin synthesis by the GDP-choline pathway. The capacity to synthesize lecithin in the lung by methylation in the human fetus and newborn allows the human to be born prematurely; rabbits and sheep lack this capacity and cannot be prematures, but die from respiratory insufficiency if born too soon.Speculation: The diagnosis of RDS can be made objectively by looking for PDME in aspirates (lung effluent). Prognosis also can be established by lack or presence of PDME. The effects of various therapies also can be assessed this way. The techniques and consideration described herein can be employed to study biochemically the effects of other stresses to lung, including oxygen toxicity and anesthesia.