Rüdiger Mario, Wendt Sebastian, Köthe Lars, Burkhardt Wolfram, Wauer Roland R, Ochs Matthias
Clinic for Neonatology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Respir Res. 2007 Jun 5;8(1):40. doi: 10.1186/1465-9921-8-40.
Repeated bronchoalveolar lavage (BAL) has been used in animals to induce surfactant depletion and to study therapeutical interventions of subsequent respiratory insufficiency. Intratracheal administration of surface active agents such as perfluorocarbons (PFC) can prevent the alveolar collapse in surfactant depleted lungs. However, it is not known how BAL or subsequent PFC administration affect the intracellular and intraalveolar surfactant pool.
Male wistar rats were surfactant depleted by BAL and treated for 1 hour by conventional mechanical ventilation (Lavaged-Gas, n = 5) or partial liquid ventilation with PF 5080 (Lavaged-PF5080, n = 5). For control, 10 healthy animals with gas (Healthy-Gas, n = 5) or PF5080 filled lungs (Healthy-PF5080, n = 5) were studied. A design-based stereological approach was used for quantification of lung parenchyma and the intracellular and intraalveolar surfactant pool at the light and electron microscopic level.
Compared to Healthy-lungs, Lavaged-animals had more type II cells with lamellar bodies in the process of secretion and freshly secreted lamellar body-like surfactant forms in the alveoli. The fraction of alveolar epithelial surface area covered with surfactant and total intraalveolar surfactant content were significantly smaller in Lavaged-animals. Compared with Gas-filled lungs, both PF5080-groups had a significantly higher total lung volume, but no other differences.
After BAL-induced alveolar surfactant depletion the amount of intracellularly stored surfactant is about half as high as in healthy animals. In lavaged animals short time liquid ventilation with PF5080 did not alter intra- or extracellular surfactant content or subtype composition.
反复支气管肺泡灌洗(BAL)已用于动物实验,以诱导表面活性剂耗竭,并研究后续呼吸功能不全的治疗干预措施。气管内给予全氟化碳(PFC)等表面活性剂可预防表面活性剂耗竭肺中的肺泡塌陷。然而,尚不清楚BAL或随后的PFC给药如何影响细胞内和肺泡内表面活性剂池。
雄性Wistar大鼠通过BAL诱导表面活性剂耗竭,并通过传统机械通气治疗1小时(灌洗-气体组,n = 5)或用PF 5080进行部分液体通气(灌洗-PF5080组,n = 5)。作为对照,研究了10只肺部充有气体的健康动物(健康-气体组,n = 5)或肺部充有PF5080的健康动物(健康-PF5080组,n = 5)。采用基于设计的体视学方法,在光镜和电镜水平上对肺实质以及细胞内和肺泡内表面活性剂池进行定量分析。
与健康肺相比,灌洗动物的II型细胞更多,其板层小体处于分泌过程中,肺泡内有新分泌的板层小体样表面活性剂形式。灌洗动物中被表面活性剂覆盖的肺泡上皮表面积分数和肺泡内表面活性剂总含量显著较小。与充气体的肺相比,两个PF5080组的肺总体积均显著更高,但无其他差异。
BAL诱导肺泡表面活性剂耗竭后,细胞内储存的表面活性剂数量约为健康动物的一半。在灌洗动物中,用PF5080进行短时间液体通气并未改变细胞内或细胞外表面活性剂含量或亚型组成。