Institute of Functional and Applied Anatomy, Medical Hannover School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
PLoS One. 2024 Mar 14;19(3):e0297889. doi: 10.1371/journal.pone.0297889. eCollection 2024.
Surfactant-specific proteins (SP) are responsible for the functional and structural integrity as well as for the stabilization of the intra-alveolar surfactant. Morphological lung maturation starts in rat lungs after birth. The aim of this study was to investigate whether the expression of the hydrophilic SP-A and the hydrophobic SP-B is associated with characteristic postnatal changes characterizing morphological lung maturation.
Stereological methods were performed on the light microscope. Using immunohistochemical and molecular biological methods (Western Blot, RT-qPCR), the SP-A and SP-B of adult rat lungs and of those with different postnatal developmental stages (3, 7, 14 and 21 days after birth) were characterized.
As signs of alveolarization the total septal surface and volume increased and the septal thickness decreased. The significantly highest relative surface fraction of SP-A labeled alveolar epithelial cells type II (AEII) was found together with the highest relative SP-A gene expression before the alveolarization (3th postnatal day). With the downregulation of SP-A gene expression during and after alveolarization (between postnatal days 7 and 14), the surface fraction of the SP-A labeled AEII also decreased, so they are lowest in adult animals. The surface fraction of SP-B labeled AEII and the SP-B gene expression showed the significantly highest levels in adults, the protein expression increased also significantly at the end of morphological lung maturation. There were no alterations in the SP-B expression before and during alveolarization until postnatal day 14. The protein expression as well as the gene expression of SP-A and SP-B correlated very well with the total surface of alveolar septa independent of the postnatal age.
The expression of SP-A and SP-B is differentially associated with morphological lung maturation and correlates with increased septation of alveoli as indirect clue for alveolarization.
表面活性物质特异性蛋白(SP)负责功能和结构的完整性以及肺泡内表面活性物质的稳定。形态学肺成熟始于大鼠出生后的肺部。本研究旨在探讨亲水性 SP-A 和疏水性 SP-B 的表达是否与形态学肺成熟的特征性产后变化有关。
在光学显微镜上进行体视学方法。使用免疫组织化学和分子生物学方法(Western Blot、RT-qPCR),对成年大鼠肺以及不同产后发育阶段(出生后第 3、7、14 和 21 天)的 SP-A 和 SP-B 进行了特征描述。
作为肺泡化的标志,总隔表面和体积增加,隔厚度减小。在肺泡化之前(第 3 天),SP-A 标记的 II 型肺泡上皮细胞(AEII)的相对表面分数显著最高,同时 SP-A 基因表达也最高。随着肺泡化过程中(出生后第 7 天至第 14 天)SP-A 基因表达的下调,SP-A 标记的 AEII 的表面分数也随之下降,因此在成年动物中最低。SP-B 标记的 AEII 的表面分数和 SP-B 基因表达水平在成年动物中最高,在形态学肺成熟末期蛋白表达也显著增加。在肺泡化之前和期间,SP-B 的表达没有变化,直到出生后第 14 天。SP-A 和 SP-B 的蛋白表达和基因表达与肺泡间隔的总表面非常相关,与产后年龄无关。
SP-A 和 SP-B 的表达与形态学肺成熟程度不同相关,并与肺泡分隔的增加相关,这是肺泡化的间接线索。