Lu Karen W, Pérez-Gil Jesús, Echaide Mercedes, Taeusch H William
Department of Pediatrics, University of California, San Francisco, CA, USA.
Biochim Biophys Acta. 2011 Oct;1808(10):2366-73. doi: 10.1016/j.bbamem.2011.06.013. Epub 2011 Jun 27.
Acute respiratory distress syndrome (ARDS) is an inflammatory condition that can be associated with capillary leak of serum into alveoli causing inactivation of surfactant. Resistance to inactivation is affected by types and concentrations of surfactant proteins, lipids, and polymers. Our aim was to investigate the effects of different combinations of these three components. A simple lipid mixture (DPPC/POPG) or a more complex lipid mixture (DPPC/POPC/POPG/cholesterol) was used. Native surfactant proteins SP-B and SP-C obtained from pig lung lavage were added either singly or combined at two concentrations. Also, non-ionic polymers polyethylene glycol and dextran and the anionic polymer hyaluronan were added either singly or in pairs with hyaluronan included. Non-ionic polymers work by different mechanisms than anionic polymers, thus the purpose of placing them together in the same surfactant mixture was to evaluate if the combination would show enhanced beneficial effects. The resulting surfactant mixtures were studied in the presence or absence of serum. A modified bubble surfactometer was used to evaluate surface activities. Mixtures that included both SP-B and SP-C plus hyaluronan and either dextran or polyethylene glycol were found to be the most resistant to inhibition by serum. These mixtures, as well as some with either SP-B or SP-C with combined polymers were as or more resistant to inactivation than native surfactant. These results suggest that improved formulations of lung surfactants are possible and may be useful in reducing some types of surfactant inactivation in treating lung injuries.
急性呼吸窘迫综合征(ARDS)是一种炎症性疾病,可能与血清毛细血管渗漏至肺泡导致表面活性剂失活有关。对失活的抵抗力受表面活性剂蛋白、脂质和聚合物的类型及浓度影响。我们的目的是研究这三种成分不同组合的效果。使用了简单脂质混合物(二棕榈酰磷脂酰胆碱/棕榈酰油酰磷脂酰甘油,DPPC/POPG)或更复杂的脂质混合物(二棕榈酰磷脂酰胆碱/棕榈酰油酰磷脂酰胆碱/棕榈酰油酰磷脂酰甘油/胆固醇,DPPC/POPC/POPG/cholesterol)。从猪肺灌洗中获得的天然表面活性剂蛋白SP - B和SP - C以单一形式或两种浓度组合添加。此外,非离子聚合物聚乙二醇和右旋糖酐以及阴离子聚合物透明质酸单独添加或与透明质酸成对添加。非离子聚合物的作用机制与阴离子聚合物不同,因此将它们置于同一表面活性剂混合物中的目的是评估这种组合是否会显示出增强的有益效果。在有或无血清的情况下研究所得的表面活性剂混合物。使用改良的气泡表面张力仪评估表面活性。发现同时包含SP - B和SP - C以及透明质酸和右旋糖酐或聚乙二醇的混合物对血清抑制最具抵抗力。这些混合物以及一些含有SP - B或SP - C与聚合物组合的混合物与天然表面活性剂相比,对失活具有相同或更高的抵抗力。这些结果表明,改进的肺表面活性剂配方是可能的,并且可能有助于减少治疗肺损伤时某些类型的表面活性剂失活。