Walther F J, Hernández-Juviel J, Bruni R, Waring A J
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.
Pediatr Res. 1998 May;43(5):666-73. doi: 10.1203/00006450-199805000-00016.
Synthetic surfactant peptides offer an opportunity to standardize the protein composition of surfactant. We tested the effect of phospholipids (PL) with synthetic full-length SP-B1-78 (B), mutant B (Bser), KL4 peptide (UCLA-KL4), and palmitoylated SP-C1-35 (C) on oxygenation and lung function in a surfactant-deficient rat model. Sixty-four adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 mL/kg, and a rate of 60/min. Their lungs were lavaged with saline until the arterial PO2 dropped below 80 torr, when 100 mg/kg surfactant was instilled. Surfactant preparations included: PL (PL surfactant), PL + 3% B (B surfactant), PL + 3% B and 1% C (BC surfactant), PL + 3% UCLA-KL4 (KL4 surfactant), PL + 3% Bser (Bser surfactant), and PL + 3% B and 1% UCLA-KL4 (BKL4 surfactant). Sixty minutes after surfactant instillation, positive end-expiratory pressure was applied for 5 min, and pressure-volume curves were determined in situ. The six surfactant preparations had a minimum surface tensions <10 mN/m on a Langmuir/Wilhelmy balance. Instillation of PL, Bser, and BKL4 surfactant increased mean arterial/alveolar PO2 (aADO2) ratios by 50-100% over postlavage values, whereas KL4 surfactant increased aADO2 ratios by 118%, B surfactant by 191%, and BC surfactant by 225%. Lung volumes at 30 cm H2O pressure were highest after treatment with BC surfactant, intermediate after B and KL4 surfactants, and lowest after BKL4, Bser, and PL surfactants. These data suggest that a surfactant preparation with a combination of synthetic B and C peptides surpasses synthetic B and KL4 surfactants in improving oxygenation and lung compliance in surfactant-deficient rats.
合成表面活性剂肽为标准化表面活性剂的蛋白质组成提供了契机。我们在表面活性剂缺乏的大鼠模型中测试了磷脂(PL)与合成全长SP-B1-78(B)、突变体B(Bser)、KL4肽(UCLA-KL4)和棕榈酰化SP-C1-35(C)对氧合和肺功能的影响。64只成年大鼠用100%氧气通气,潮气量为7.5 mL/kg,呼吸频率为60次/分钟。用盐水对其肺部进行灌洗,直到动脉血氧分压降至80托以下,此时注入100 mg/kg表面活性剂。表面活性剂制剂包括:PL(PL表面活性剂)、PL + 3%B(B表面活性剂)、PL + 3%B和1%C(BC表面活性剂)、PL + 3%UCLA-KL4(KL4表面活性剂)、PL + 3%Bser(Bser表面活性剂)以及PL + 3%B和1%UCLA-KL4(BKL4表面活性剂)。注入表面活性剂60分钟后,施加呼气末正压5分钟,并在原位测定压力-容积曲线。这六种表面活性剂制剂在Langmuir/威尔海姆天平上的最小表面张力<10 mN/m。注入PL、Bser和BKL4表面活性剂后,平均动脉/肺泡血氧分压(aADO2)比值比灌洗后的值增加了50%-100%,而KL4表面活性剂使aADO2比值增加了118%,B表面活性剂增加了191%,BC表面活性剂增加了225%。在30 cm H2O压力下的肺容积,用BC表面活性剂治疗后最高,用B和KL4表面活性剂治疗后居中,用BKL4、Bser和PL表面活性剂治疗后最低。这些数据表明,含有合成B肽和C肽组合的表面活性剂制剂在改善表面活性剂缺乏大鼠的氧合和肺顺应性方面优于合成B和KL4表面活性剂。