Savla Ushma, Olson Lars E, Waters Christopher M
Department of Biomedical Engineering, Northwestern University, Chicago, Illinois 60208, USA.
J Appl Physiol (1985). 2004 Feb;96(2):566-74. doi: 10.1152/japplphysiol.00510.2003.
The repair of airway epithelium after injury is crucial in restoring epithelial barrier integrity. Because the airways are stretched and compressed due to changes in both circumferential and longitudinal dimensions during respiration and may be overdistended during mechanical ventilation, we investigated the effect of cyclic strain on the repair of epithelial wounds. Both cyclic elongation and compression significantly slowed repair, with compression having the greatest effect. We developed a mathematical model of the mechanisms involved in airway epithelial cell wound closure. The model focuses on the differences in spreading, migration, and proliferation with cyclic strain by using separate parameters for each process and incorporating a time delay for the mitotic component. Numerical solutions of model equations determine the shape of the diffusive wave solutions of cell density that correspond to the influx of cells into the wound during the initial phase of reepithelialization. Model simulations were compared with experimental measurements of cell density and the rate of wound closure, and parameters were determined based on measurements from airway epithelial cells from several different sources. The contributions of spreading, migration, and mitosis were investigated both numerically and experimentally by using cytochalasin D to inhibit cell motility and mitomycin C to inhibit proliferation.
损伤后气道上皮的修复对于恢复上皮屏障完整性至关重要。由于在呼吸过程中气道会因周向和纵向尺寸的变化而受到拉伸和压缩，并且在机械通气期间可能会过度扩张，我们研究了周期性应变对上皮伤口修复的影响。周期性伸长和压缩均显著延缓修复，其中压缩的影响最大。我们建立了一个涉及气道上皮细胞伤口闭合机制的数学模型。该模型通过为每个过程使用单独的参数并纳入有丝分裂成分的时间延迟，着重研究了周期性应变下细胞铺展、迁移和增殖的差异。模型方程的数值解确定了细胞密度扩散波解的形状，该形状对应于再上皮化初始阶段细胞流入伤口的情况。将模型模拟结果与细胞密度和伤口闭合速率的实验测量值进行比较，并根据来自几种不同来源的气道上皮细胞的测量值确定参数。通过使用细胞松弛素D抑制细胞运动性和丝裂霉素C抑制增殖，从数值和实验两方面研究了铺展、迁移和有丝分裂的作用。
