Laubach Victor E, Sharma Ashish K
Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Curr Opin Organ Transplant. 2016 Jun;21(3):246-52. doi: 10.1097/MOT.0000000000000304.
Lungs are extremely susceptible to injury, and despite advances in surgical management and immunosuppression, outcomes for lung transplantation are the worst of any solid organ transplant. The success of lung transplantation is limited by high rates of primary graft dysfunction because of ischemia-reperfusion injury characterized by robust inflammation, alveolar damage, and vascular permeability. This review will summarize major mechanisms of lung ischemia-reperfusion injury with a focus on the most recent findings in this area.
Over the past 18 months, numerous studies have described strategies to limit lung ischemia-reperfusion injury in experimental settings, which often reveal mechanistic insight. Many of these strategies involved the use of various antioxidants, anti-inflammatory agents, mesenchymal stem cells, and ventilation with gaseous molecules. Further advancements have been achieved in understanding mechanisms of innate immune cell activation, neutrophil infiltration, endothelial barrier dysfunction, and oxidative stress responses.
Methods for prevention of primary graft dysfunction after lung transplant are urgently needed, and understanding mechanisms of ischemia-reperfusion injury is critical for the development of novel and effective therapeutic approaches. In doing so, both acute and chronic outcomes of lung transplant recipients will be significantly improved.
肺极易受到损伤，尽管在手术管理和免疫抑制方面取得了进展，但肺移植的结果是所有实体器官移植中最差的。肺移植的成功受到原发性移植功能障碍高发生率的限制，这种障碍是由缺血再灌注损伤引起的，其特征是强烈的炎症、肺泡损伤和血管通透性增加。本综述将总结肺缺血再灌注损伤的主要机制，并重点关注该领域的最新研究结果。
在过去18个月里，许多研究描述了在实验环境中限制肺缺血再灌注损伤的策略，这些策略往往揭示了机制方面的见解。其中许多策略涉及使用各种抗氧化剂、抗炎剂、间充质干细胞以及用气态分子进行通气。在理解固有免疫细胞激活、中性粒细胞浸润、内皮屏障功能障碍和氧化应激反应的机制方面取得了进一步进展。
迫切需要预防肺移植后原发性移植功能障碍的方法，了解缺血再灌注损伤的机制对于开发新的有效治疗方法至关重要。这样做将显著改善肺移植受者的急性和慢性结局。
