Lu Karen W, Taeusch H William, Clements John A
Department of Pediatrics, University of California, San Francisco, California 94110, USA.
Exp Lung Res. 2013 May-Jun;39(4-5):191-200. doi: 10.3109/01902148.2013.791893. Epub 2013 May 3.
Surfactants in current clinical use are largely ineffective in treating acute lung injury (ALI)/ acute respiratory distress syndrome. In part, this ineffectiveness is due to inactivation of surfactant by serum leakage into the alveoli. Previously, we reported that adding hyaluronan and some nonionic polymers to synthetic lipids combined with native SP-B and SP-C enhanced surface activity. In this study, we first tested two therapeutic lung surfactants and then retested after adding hyaluronan, polyethylene glycol or dextran alone or in two-polymer combinations including hyaluronan in the absence or presence of serum. Surface activities were measured in a modified bubble surfactometer. Results indicate that the inhibition threshold (defined as the amount of serum required to produce a minimum surface tension above 10 mN/m after 5 minutes of cycling) was 35 times higher with hyaluronan plus dextran added to Infasurf than with Infasurf alone, and better than all other mixtures tested. The threshold for Survanta with hyaluronan plus polyethylene glycol was 7 times higher than Survanta alone. We next tested selected surfactant mixtures in an animal model that mimicked ALI. All measurements of lung function showed significant improvement (P ≤ .05) with hyaluronan, or with hyaluronan and dextran added to Infasurf compared to Infasurf alone. Also, for these two groups, lung function was still improving at the end of the experiment. We conclude that certain polymers added to clinical surfactants can greatly increase resistance to inactivation in vitro, while in vivo, both Infasurf mixtures containing hyaluronan tended to normalize measures of lung function unlike other mixtures tested.
目前临床使用的表面活性剂在治疗急性肺损伤（ALI）/急性呼吸窘迫综合征方面大多无效。部分原因在于血清漏入肺泡会使表面活性剂失活。此前，我们报道过在合成脂质中添加透明质酸和一些非离子聚合物，并结合天然的表面活性蛋白B（SP - B）和表面活性蛋白C（SP - C）可增强表面活性。在本研究中，我们首先测试了两种治疗性肺表面活性剂，然后在单独添加透明质酸、聚乙二醇或右旋糖酐，或添加包括透明质酸在内的两种聚合物组合（有无血清存在的情况下）后再次进行测试。在改良的气泡表面张力测定仪中测量表面活性。结果表明，在Infasurf中添加透明质酸加右旋糖酐后的抑制阈值（定义为循环5分钟后产生最小表面张力高于10 mN/m所需的血清量）比单独使用Infasurf时高35倍，且优于所有其他测试混合物。在Survanta中添加透明质酸加聚乙二醇后的阈值比单独使用Survanta高7倍。接下来，我们在模拟ALI的动物模型中测试了选定的表面活性剂混合物。与单独使用Infasurf相比，添加透明质酸或添加透明质酸和右旋糖酐的Infasurf在所有肺功能测量中均显示出显著改善（P≤0.05）。此外，对于这两组，在实验结束时肺功能仍在改善。我们得出结论，向临床表面活性剂中添加某些聚合物可在体外大大增加对失活的抵抗力，而在体内，与其他测试混合物不同，两种含有透明质酸的Infasurf混合物往往能使肺功能指标恢复正常。
