Brunelli Luca, Hamilton Eric, Davis Jonathan M, Koo Hshi-Chi, Joseph Ansamma, Kazzaz Jeffrey A, Wolfson Marla R, Shaffer Thomas H
Division of Neonatology , Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Pediatr Res. 2006 Jul;60(1):65-70. doi: 10.1203/01.pdr.0000219392.73509.70. Epub 2006 May 11.
Previous studies suggest acute lung injury (ALI) in premature newborns is associated with relative deficiency of antioxidant enzymes that may be ameliorated by recombinant human superoxide dismutase (rhSOD). Perfluorochemicals (PFCs) are distributed homogeneously and support gas exchange in diseased lungs. We investigated whether PFCs could provide an effective delivery system for rhSOD. Juvenile rabbits were lung-lavaged, treated with surfactant, and randomized: group I: fluorescently labeled rhSOD (5 mg/kg in 2 mL/kg saline); group II: fluorescently labeled rhSOD (5 mg/kg in 18 mL/kg PFC). Animals were ventilated with oxygen for 4 h; the lungs were harvested for analysis of SOD distribution and oxidative injury. Cardiopulmonary indices remained stable and similar between groups. Qualitative assessment (QA) showed a more homogeneous lung SOD distribution in group II and a better histologic profile. QA of lung SOD distribution showed significant increase in SOD concentrations in group II (7.37 +/- 1.54 microg/mg protein) compared with group I (1.65 +/- 0.23 microg/mg protein). Oxidative injury as assessed by normalized protein carbonyl was 149.1 +/- 26.8% SEM in group II compared with 200.5 +/- 7.3% SEM in group I. Plasma SOD was significantly higher in group II. Administration of rhSOD with or without PFCs does not compromise cardiovascular function or impede lung recovery after ALI. PFCs enhance rhSOD delivery to the lungs by 400% while decreasing lung oxidative damage by 25% compared with rhSOD alone. These data suggest that PFCs optimize lung rhSOD delivery and might enhance the beneficial effects of rhSOD in preventing acute and chronic lung injury.
先前的研究表明，早产新生儿的急性肺损伤（ALI）与抗氧化酶相对缺乏有关，重组人超氧化物歧化酶（rhSOD）可能会改善这种情况。全氟化合物（PFCs）分布均匀，可支持患病肺部的气体交换。我们研究了PFCs是否能为rhSOD提供有效的递送系统。对幼年兔进行肺灌洗、用表面活性剂治疗并随机分组：第一组：荧光标记的rhSOD（5mg/kg溶于2mL/kg盐水中）；第二组：荧光标记的rhSOD（5mg/kg溶于18mL/kg PFC中）。动物用氧气通气4小时；收获肺组织以分析SOD分布和氧化损伤。两组之间的心肺指标保持稳定且相似。定性评估（QA）显示，第二组肺SOD分布更均匀，组织学特征更好。肺SOD分布的QA显示，第二组的SOD浓度（7.37±1.54μg/mg蛋白质）显著高于第一组（1.65±0.23μg/mg蛋白质）。通过标准化蛋白质羰基评估的氧化损伤，第二组为149.1±26.8%SEM，而第一组为200.5±7.3%SEM。第二组的血浆SOD显著更高。rhSOD联合或不联合PFCs给药均不会损害心血管功能或阻碍ALI后的肺恢复。与单独使用rhSOD相比，PFCs可使rhSOD向肺部的递送提高400%，同时使肺氧化损伤降低25%。这些数据表明，PFCs可优化肺rhSOD递送，并可能增强rhSOD在预防急性和慢性肺损伤方面的有益作用。
