Developing artificial surfactant containing membrane-fusing substance and application for meconium aspiration syndrome

猪表面活性剂（200 mg/kg）可使实验性胎粪吸入综合征大鼠PaO_2由100 mmHg提高到300 mmHg，但作用是短暂的。表面活性剂或肺灌洗中添加葡聚糖显著增强了治疗效果（P<0.05）；PaO_2维持在300 mraHg左右180 min。酸化乳致实验性急性呼吸窘迫综合征大鼠，吸入表面活性剂雾化30 min后，PaO_2由90 mmHg升高至300 mmHg，但很快降至100 mmHg以下。然而，吸入雾化右旋糖酐使PaO_2维持在300 mmHg左右。结果表明，葡聚糖可显著改善表面活性剂替代的治疗效果。研制了一种与表面活性剂蛋白C （SP-C）相似的合成肽，并用于合成表面活性剂（SS）。SS的最小和最大表面张力（γmax）分别约为2 mN/m和40 mN/m。γmax显著高于猪表面活性剂。右旋糖酐的加入使γmax降低到约30 mN/m （NS）。猪表面活性剂)。未成熟新生兔接受SS（约10 ml/kg）的潮气量（TV）显著优于仅接受磷脂的潮气量（TV）。添加葡聚糖后，SS的潮气量达到15 ml/kg，但仍低于表面活性剂普鲁氨酸。在对肺泡蛋白沉积症患者SP-C的分析中，未成熟新生兔的二聚体SP-C比单体SP-C产生更大的TV，与接受正常SP-C的TV没有显著差异。在合成表面活性剂中加入葡聚糖或使用二聚体SP-C都值得进一步实验开发合成表面活性剂。

In rats with experimental meconium aspiration syndrome, administration of porcine surfactant (200 mg/kg) improved the PaO_2 from 100 mmHg to 300 mmHg, but the effect was only transient. Supplementation of dextran to surfactant or lung lavage significantly (P<0.05) strengthened the therapeutic effects; the PaO_2 was maintained at about 300 mraHg for 180 min. In rats with experimental acute respiratory distress syndrome caused by acidified milk, inhalation of aerosolized surfactant for 30 min increased the PaO_2 from 90 mmHg to 300 mmHg, but the PaO_2 soon decreased to below 100 mmHg. However, inhalation of aerosolized dextran maintained the PaO_2 at about 300 mmHg. These results indicated hat dextran significantly improves therapeutic effects of surfactant replacement.A synthetic peptide similar to surfactant protein C (SP-C) was developed, and used to prepare synthetic surfactant (SS). The minimum and maximum (γmax) surface tension of SS was about 2 mN/m and 40 mN/m, respectively. The γmax was significantly higher than that of porcine surfactant. Addition of dextran to SS reduced the γmax to about 30 mN/m (NS. vs. porcine surfactant). Tidal volume (TV) of immature newborn rabbits receiving SS (about 10 ml/kg) was significantly better than that receiving phospholipids only. Addtion of dextran to SS impveed the tidal volume to 15 ml/kg, which was still less than procine surfactant. In analyses of SP-C derived from patients with pulmonary alveolar proteinosis, dimeric SP-C yielded larger TV than monomeric form SP-C in immature newborn rabbits, and the TV was not significantly different from that receiving normal SP-C. Addition of dextran to synthetic surfactant or using dimeric SP-C warrants further experiment to develop synthetic surfactant.