Pérez-Bravo David, Myti Despoina, Mižíková Ivana, Pfeffer Tilman, Surate Solaligue David E, Nardiello Claudio, Vadász István, Herold Susanne, Seeger Werner, Ahlbrecht Katrin, Morty Rory E
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Parkstrasse 1, 60231, Bad Nauheim, Germany.
Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Aulweg 123, 35394, Giessen, Germany.
Histochem Cell Biol. 2021 Feb;155(2):203-214. doi: 10.1007/s00418-020-01951-0. Epub 2020 Dec 29.
The morphometric analysis of lung structure using the principles of stereology has emerged as a powerful tool to describe the structural changes in lung architecture that accompany the development of lung disease that is experimentally modelled in adult mice. These stereological principles are now being applied to the study of the evolution of the lung architecture over the course of prenatal and postnatal lung development in mouse neonates and adolescents. The immature lung is structurally and functionally distinct from the adult lung, and has a smaller volume than does the adult lung. These differences have raised concerns about whether the inflation fixation of neonatal mouse lungs with the airway pressure (P) used for the inflation fixation of adult mouse lungs may cause distortion of the neonatal mouse lung structure, leading to the generation of artefacts in subsequent analyses. The objective of this study was to examine the impact of a P of 10, 20 and 30 cmHO on the estimation of lung volumes and stereologically assessed parameters that describe the lung structure in developing mouse lungs. The data presented demonstrate that low P (10 cmHO) leads to heterogeneity in the unfolding of alveolar structures within the lungs, and that high P (30 cmHO) leads to an overestimation of the lung volume, and thus, affects the estimation of volume-dependent parameters, such as total alveoli number and gas-exchange surface area. Thus, these data support the use of a P of 20 cmHO for inflation fixation in morphometric studies on neonatal mouse lungs.
利用体视学原理对肺结构进行形态计量分析，已成为一种强大的工具，用于描述在成年小鼠中通过实验模拟的肺部疾病发展过程中肺结构的变化。现在，这些体视学原理正被应用于研究小鼠新生儿和青少年在产前和产后肺发育过程中肺结构的演变。未成熟的肺在结构和功能上与成年肺不同，且体积比成年肺小。这些差异引发了人们对使用成年小鼠肺充气固定时的气道压力（P）对新生小鼠肺进行充气固定是否会导致新生小鼠肺结构变形，从而在后续分析中产生假象的担忧。本研究的目的是检验10、20和30厘米水柱的压力对发育中小鼠肺的肺容积估计以及描述肺结构的体视学评估参数的影响。所呈现的数据表明，低压力（10厘米水柱）会导致肺内肺泡结构展开的异质性，而高压力（30厘米水柱）会导致肺容积的高估，进而影响对与容积相关参数的估计，如肺泡总数和气体交换表面积。因此，这些数据支持在新生小鼠肺的形态计量学研究中使用20厘米水柱的压力进行充气固定。
