Bernhard W, Wang J Y, Tschernig T, Tümmler B, Hedrich H J, von der Hardt H
Department of Pediatric Pulmonology, Hannover Medical School, Germany.
Thorax. 1997 Aug;52(8):723-30. doi: 10.1136/thx.52.8.723.
Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftrm1HGU/m1HGU mouse.
The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls.
BAL fluid of cftrm1HGU/m1HGU mice contained 1.02 (95% confidence interval (CI) 0.89 to 1.16) mumol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and C3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) mumol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftrm1HGU/m1HGU mice were increased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in cftrm1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftrm1HGU/m1HGU mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function.
In cftrm1HGU/m1HGU mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.
进行性肺功能障碍是囊性纤维化（CF）的一个特征性症状，与气道中表面活性物质磷脂的功能损害和生化改变有关。然而，CF肺中表面活性物质的改变是继发于肺损伤还是在慢性感染和炎症开始之前就已存在，这一基本问题在CF患者中尚未得到解决，但现在可以在表现出气道基本缺陷的CF小鼠中进行研究。因此，开展了一项研究，以调查未感染的cftrm1HGU/m1HGU小鼠肺表面活性物质的储备量、组成和功能。
通过高效液相色谱法（HPLC）测定支气管肺泡灌洗（BAL）液和灌洗肺中磷脂类和磷脂酰胆碱分子种类的含量及组成。通过酶联免疫吸附测定法（ELISA）测定BAL液中表面活性蛋白A（SP-A）的水平，并通过差速超速离心法从BAL液中分离出用于功能测量的表面活性物质。通过脉动气泡表面张力仪技术评估表面活性物质的平衡表面张力和最小表面张力。MF1、BALB/c、C57/BL6和C3H/He小鼠作为对照。
cftrm1HGU/m1HGU小鼠的BAL液中含有1.02（95%置信区间（CI）0.89至1.16）μmol磷脂和259（239至279）ng SP-A。MF1、BALB/c、C57BL/6和C3H/He小鼠的BAL液中分别含有0.69（0.63至0.75）、0.50（0.42至0.57）、0.52（0.40至0.64）和0.45（0.27至0.63）μmol磷脂。校正小鼠品系不同体重后，cftrm1HGU/m1HGU小鼠BAL液中的磷脂水平分别比对照组增加了64（52至76）%、60（39至89）%、72（45至113）%和92（49至163）%。与对照组相比，cftrm1HGU/m1HGU小鼠BAL液中SP-A的含量以及BAL液和肺组织中磷脂以及磷脂酰胆碱分子种类的组成均未改变。cftrm1HGU/m1HGU小鼠BAL液中磷脂的增加是由于大聚集体比例增加，而这些大聚集体表现出正常的表面张力功能。
在cftrm1HGU/m1HGU小鼠中，肺泡腔中磷脂储备量增加扰乱了表面活性物质的稳态。
