Mbagwu N, Bruni R, Hernández-Juviel J M, Waring A J, Walther F J
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, California.
Mol Genet Metab. 1999 Jan;66(1):40-8. doi: 10.1006/mgme.1998.2788.
Surfactant can be inhibited in vivo by plasma proteins invading the alveolar space during acute lung injury. The resistance to protein inhibition of surfactant preparations with various synthetic surfactant proteins B and C (B and C) was tested in preterm rabbits. Surfactants consisted of a palmitic acid containing phospholipid mixture (PL) with full-length SP-B peptide (B1-78), one of two SP-B mutants (Bserine and BR236C), the synthetic SP-B mimic KL4 (UCLA-KL4), a natural SP-B (Bbovine), synthetic palmitoylated SP-C peptide (C1-35), a combination of B1-78 + C1-35, a combination of BR236C + C1-35, and the clinical surfactant Survanta. Preterm rabbits born at 28 days of gestation were ventilated and received 100 mg/kg of albumin intratracheally at 30 min and 100 mg/kg of surfactant at 45 min after birth. Dynamic lung compliance (tidal volume/mean airway pressure) decreased from 0.82 to 0.57 mL/kg/cm H2O after albumin instillation and to 0.43 mL/kg/cm H2O over a 60-min period after saline placebo. Treatment with B1-78 + C1-35 and BR236C + C1-35 surfactant and Survanta returned dynamic compliance to prealbumin values, B1-78, BR236C, Bbovine, and C1-35 surfactant stabilized dynamic compliance, but PL, Bserine, and UCLA-KL4 surfactant were unable to prevent a further deterioration in dynamic compliance. These data suggest that a combination of synthetic surfactant peptides B1-78 and C1-35 and the clinical surfactant Survanta confer a high degree of resistance to surfactant inhibition by human albumin in ventilated preterm rabbits.
在急性肺损伤期间,血浆蛋白侵入肺泡腔可在体内抑制表面活性剂。在早产兔中测试了各种合成表面活性剂蛋白B和C(B和C)制剂对蛋白抑制表面活性剂的抗性。表面活性剂由含棕榈酸的磷脂混合物(PL)与全长SP-B肽(B1-78)、两种SP-B突变体之一(B丝氨酸和BR236C)、合成SP-B模拟物KL4(加州大学洛杉矶分校-KL4)、天然SP-B(B牛)、合成棕榈酰化SP-C肽(C1-35)、B1-78 + C1-35组合、BR236C + C1-35组合以及临床表面活性剂固尔苏组成。妊娠28天出生的早产兔进行通气,在出生后30分钟经气管内给予100mg/kg白蛋白,在45分钟给予100mg/kg表面活性剂。白蛋白滴注后动态肺顺应性(潮气量/平均气道压)从0.82降至0.57mL/kg/cm H2O,在生理盐水安慰剂给药后60分钟内降至0.43mL/kg/cm H2O。用B1-78 + C1-35和BR236C + C1-35表面活性剂以及固尔苏治疗可使动态顺应性恢复到白蛋白给药前的值,B1-78、BR236C、B牛和C1-35表面活性剂可稳定动态顺应性,但PL、B丝氨酸和加州大学洛杉矶分校-KL4表面活性剂无法防止动态顺应性进一步恶化。这些数据表明,合成表面活性剂肽B1-78和C1-35与临床表面活性剂固尔苏的组合在通气早产兔中赋予了对人白蛋白抑制表面活性剂的高度抗性。