Khan Mohammad Afzal, Bhusal Subarna, Lau Christine L, Krupnick Alexander Sasha
Department of Surgery, University of Maryland, Baltimore, MA, United States.
Front Immunol. 2025 May 14;16:1567657. doi: 10.3389/fimmu.2025.1567657. eCollection 2025.
Lung transplantation (LTx) offers a last resort for patients battling end-stage lung disease. Even though short-term survival has improved, these patients still face several long-term challenges, such as chronic rejection and ischemic bronchial anastomosis. In lung transplant recipients, the bronchial anastomosis is prone to complications-such as poor wound healing, necrosis, stenosis, and dehiscence-due to the marginal blood supply at this site. During peri-LTx, hypoxia and ischemia stimulate fibrotic and inflammatory cytokines at anastomotic sites, leading to abnormal collagen production and excessive granulation, which impair wound healing. Despite meticulous techniques, bronchial anastomosis remains a major cause of morbidity and mortality among lung transplant recipients. After LTx, most bronchial complications are attributed to ischemic insult since normal bronchial blood flow is disrupted, and bronchial revascularization usually takes two to four weeks, making the anastomotic bronchial vessels dependent on pulmonary artery circulation. It is clear that hypoxia, inflammation, oxidative stress, and extracellular matrix remodeling play critical roles in bronchial complications, but there is no small animal model to study them. In the context of LTx, mouse tracheal models are essential tools for studying bronchial complications, particularly ischemia, fibrosis, and stenosis, as well as evaluating potential therapeutic interventions. A well-established mouse model of orthotopic tracheal transplantation (OTT) mimics the anastomosis of the bronchi and the subsequent microvascular injury, providing a pathological correlation with anastomotic complications. A series of previous studies using the OTT model explored the microvascularization, ischemia-reperfusion, airway epithelial injury, and fibrotic remodeling effects after airway anastomosis. This review describes OTT as a model of airway anastomotic complications, which is crucial for understanding the immunological and molecular pathways as seen in clinical bronchial anastomoses, as well as improving anastomotic healing and reducing complications through targeted therapeutic strategies.
肺移植（LTx）为终末期肺病患者提供了最后的治疗手段。尽管短期生存率有所提高，但这些患者仍面临一些长期挑战，如慢性排斥反应和缺血性支气管吻合。在肺移植受者中，由于该部位血供边缘，支气管吻合容易出现并发症，如伤口愈合不良、坏死、狭窄和裂开。在围肺移植期，缺氧和缺血会刺激吻合部位的纤维化和炎性细胞因子，导致胶原蛋白产生异常和肉芽组织过度增生，从而损害伤口愈合。尽管技术精细，但支气管吻合仍是肺移植受者发病和死亡的主要原因。肺移植后，大多数支气管并发症归因于缺血性损伤，因为正常的支气管血流被中断，支气管再血管化通常需要两到四周，使得吻合部位的支气管血管依赖于肺动脉循环。显然，缺氧、炎症、氧化应激和细胞外基质重塑在支气管并发症中起关键作用，但尚无小动物模型来研究这些问题。在肺移植背景下，小鼠气管模型是研究支气管并发症，特别是缺血、纤维化和狭窄，以及评估潜在治疗干预措施的重要工具。成熟的原位气管移植（OTT）小鼠模型模拟了支气管吻合及随后的微血管损伤，为吻合并发症提供了病理相关性。此前一系列使用OTT模型的研究探讨了气道吻合后的微血管化、缺血再灌注、气道上皮损伤和纤维化重塑效应。本综述将OTT描述为气道吻合并发症模型，这对于理解临床支气管吻合中所见的免疫和分子途径，以及通过靶向治疗策略改善吻合口愈合和减少并发症至关重要。
