School of Pharmacy and Allied Health Sciences, St John's University, Queens, NY 11439, USA.
Int J Mol Sci. 2024 Oct 2;25(19):10613. doi: 10.3390/ijms251910613.
Pulmonary emphysema involves progressive destruction of alveolar walls, leading to enlarged air spaces and impaired gas exchange. While the precise mechanisms responsible for these changes remain unclear, there is growing evidence that the extracellular matrix plays a critical role in the process. An essential feature of pulmonary emphysema is damage to the elastic fiber network surrounding the airspaces, which stores the energy needed to expel air from the lungs. The degradation of these fibers disrupts the mechanical forces involved in respiration, resulting in distension and rupture of alveolar walls. While the initial repair process mainly consists of elastin degradation and resynthesis, continued alveolar wall injury may be associated with increased collagen deposition, resulting in a mixed pattern of emphysema and interstitial fibrosis. Due to the critical role of elastic fiber injury in pulmonary emphysema, preventing damage to this matrix component has emerged as a potential therapeutic strategy. One treatment approach involves the intratracheal administration of hyaluronan, a polysaccharide that prevents elastin breakdown by binding to lung elastic fibers. In clinical trials, inhalation of aerosolized HA decreased elastic fiber injury, as measured by the release of the elastin-specific cross-linking amino acids, desmosine, and isodesmosine. By protecting elastic fibers from enzymatic and oxidative damage, aerosolized HA could alter the natural history of pulmonary emphysema, thereby reducing the risk of respiratory failure.
肺气肿涉及肺泡壁的进行性破坏，导致气腔扩大和气体交换受损。虽然导致这些变化的确切机制尚不清楚，但越来越多的证据表明细胞外基质在该过程中起着关键作用。肺气肿的一个重要特征是破坏围绕气腔的弹性纤维网络，该网络储存着从肺部排出空气所需的能量。这些纤维的降解破坏了呼吸过程中涉及的机械力，导致肺泡壁膨胀和破裂。虽然最初的修复过程主要包括弹性蛋白的降解和再合成，但持续的肺泡壁损伤可能与胶原沉积增加有关，导致肺气肿和间质纤维化的混合模式。由于弹性纤维损伤在肺气肿中的关键作用，防止这种基质成分的损伤已成为一种潜在的治疗策略。一种治疗方法涉及气管内给予透明质酸，这是一种多糖，通过与肺弹性纤维结合来防止弹性蛋白的分解。在临床试验中，吸入雾化 HA 可减少弹性纤维损伤，这可通过释放弹性蛋白特异性交联氨基酸，即脱氧木糖和异脱氧木糖来衡量。通过保护弹性纤维免受酶和氧化损伤，雾化 HA 可以改变肺气肿的自然病史，从而降低呼吸衰竭的风险。
