Holm B A, Venkitaraman A R, Enhorning G, Notter R H
Department of Gynecology/Obstetrics, State University of New York, Buffalo 14222.
Chem Phys Lipids. 1990 Feb;52(3-4):243-50. doi: 10.1016/0009-3084(90)90120-g.
The biophysical activity and inhibition of a series of synthetic surfactant mixtures was studied and correlated with physiological effectiveness in restoring pressure-volume (P-V) mechanics of excised lungs. Results showed that several simple mixtures of dipalmitoyl phosphatidylcholine (DPPC) with fatty acids or diacylglycerols could be formulated to give good adsorption facility and dynamic surface tension lowering to less than 1 mN/m in pulsating bubble measurements at 37 degrees C. However, although biophysical activity approached that of natural lung surfactant (LS) and a related surfactant extract (CLSE) under normal conditions, surface properties were sharply inhibited by relatively small amounts of the plasma protein albumin (2 mg/ml) with minimum surface tensions greater than 30 nM/m even at high surfactant concentrations (5-20 mg lipids/ml). This sensitivity to biophysical inhibition was markedly increased compared to LS and CLSE, and had direct consequences for physiological efficacy: in spite of initially high activity, synthetic surfactants did not exert beneficial effects on P-V mechanics when instilled into surfactant-deficient excised rat lungs. Endogenous protein material was shown to be present upon surfactant recovery by lavage, and bubble measurements confirmed surface activity well below pre-instillation levels. Moreover, full biophysical activity was restored when lavage fluid was extracted to separate the synthetic surfactants from endogenous inhibitors. These results show that it is important to define relative sensitivity to biophysical inhibition in the development of effective lung surfactant substitutes. In addition, the existence of inhibition effects can generate an apparent lack of correspondence between initial biophysical activity and ultimate physiological actions of exogenous surfactant mixtures.
研究了一系列合成表面活性剂混合物的生物物理活性及其抑制作用，并将其与恢复离体肺压力-容积（P-V）力学的生理有效性相关联。结果表明，几种由二棕榈酰磷脂酰胆碱（DPPC）与脂肪酸或二酰基甘油组成的简单混合物，在37℃的脉动气泡测量中，可被配制成具有良好的吸附能力且能将动态表面张力降低至1 mN/m以下。然而，尽管在正常条件下生物物理活性接近天然肺表面活性剂（LS）和相关表面活性剂提取物（CLSE），但相对少量的血浆蛋白白蛋白（2 mg/ml）就能显著抑制其表面性质，即使在高表面活性剂浓度（5 - 20 mg脂质/ml）下，最小表面张力仍大于30 nM/m。与LS和CLSE相比，这种对生物物理抑制的敏感性显著增加，并且对生理功效有直接影响：尽管最初活性较高，但将合成表面活性剂注入缺乏表面活性剂的离体大鼠肺中时，对P-V力学并没有产生有益影响。通过灌洗回收表面活性剂时，发现存在内源性蛋白质物质，气泡测量证实表面活性远低于灌洗前水平。此外，当对灌洗液进行提取以将合成表面活性剂与内源性抑制剂分离时，完全恢复了生物物理活性。这些结果表明，在开发有效的肺表面活性剂替代品时，确定对生物物理抑制的相对敏感性很重要。此外，抑制作用的存在可能导致外源性表面活性剂混合物的初始生物物理活性与最终生理作用之间明显缺乏对应关系。
