Moison R M, Palinckx J J, Roest M, Houdkamp E, Berger H M
Department of Paediatrics, University Hospital of Leiden, The Netherlands.
Lancet. 1993 Jan 9;341(8837):79-82. doi: 10.1016/0140-6736(93)92557-a.
Respiratory distress syndrome of the preterm baby is believed to be caused by a deficiency of pulmonary surfactant and leakage of plasma into the alveolar spaces. Since the two pathogenetic factors seem to be inter-related, we postulated that peroxidation of surfactant by plasma iron could be the linking mechanism. We obtained cord blood samples from 22 preterm babies (mean gestational age 32.2 [SD 2.7] weeks) and 24 term babies (40.1 [1.6] weeks), and venous blood samples from 18 healthy adults. No adult had detectable non-protein-bound iron in the plasma, but 10/21 (48%) preterm babies and 6/24 (25%) term babies had detectable concentrations (rate difference 23% [95% Cl -5 to 51%], p = 0.20). Transferrin and haptoglobin concentrations were higher and free haemoglobin concentrations lower in adults than in babies (p < 0.005). Only transferrin differed significantly between term and preterm babies. Plasma from all 18 adults and from 23 (96%) term babies inhibited iron-catalysed lipid peroxidation of pulmonary surfactant liposomes. By contrast, plasma from 11 (50%) preterm babies stimulated such peroxidation (difference in stimulation rate 46% [20-71%], p < 0.005 for preterm vs term babies); the ability to stimulate peroxidation was related to the presence of non-protein-bound iron (p < 0.001). Peroxidation decreased in the babies when apotransferrin was added to plasma and in all subjects when alpha-tocopherol was incorporated into the surfactant liposomes. Lipid peroxidation of surfactant may contribute to the pathogenesis of respiratory distress syndrome. Possible therapeutic approaches are increasing babies' iron-binding capacity by plasma transfusions and increasing the antioxidant capacity of commercial surfactant.
早产儿呼吸窘迫综合征被认为是由肺表面活性物质缺乏和血浆漏入肺泡腔所致。由于这两个致病因素似乎相互关联，我们推测血浆铁对表面活性物质的过氧化作用可能是其联系机制。我们采集了22例早产儿（平均胎龄32.2 [标准差2.7]周）和24例足月儿（40.1 [1.6]周）的脐带血样本，以及18名健康成年人的静脉血样本。所有成年人血浆中均未检测到可检测到的非蛋白结合铁，但10/21（48%）的早产儿和6/24（25%）的足月儿有可检测到的浓度（率差23% [95%可信区间 -5至51%]，p = 0.20）。成年人的转铁蛋白和触珠蛋白浓度高于婴儿，而游离血红蛋白浓度低于婴儿（p < 0.005）。仅转铁蛋白在足月儿和早产儿之间有显著差异。所有18名成年人以及23例（96%）足月儿的血浆均抑制肺表面活性物质脂质体的铁催化脂质过氧化。相比之下，11例（50%）早产儿的血浆刺激了这种过氧化作用（刺激率差异46% [20 - 71%]，早产儿与足月儿相比p < 0.005）；刺激过氧化的能力与非蛋白结合铁的存在有关（p < 0.001）。当向血浆中添加脱铁转铁蛋白时，婴儿的过氧化作用降低，而当将α-生育酚掺入表面活性物质脂质体时所有受试者的过氧化作用均降低。表面活性物质的脂质过氧化可能导致呼吸窘迫综合征的发病机制。可能的治疗方法包括通过输血增加婴儿的铁结合能力以及提高商业表面活性物质的抗氧化能力。
