肺移植动物模型:损伤、保护及免疫反应

An animal model of lung transplantation: damage, protection and immune response

背景:建立具有可操作性的肺移植动物模型对发展临床肺移植具有重要意义。目的:对肺移植临床前期研究的肺移植动物建立中的动物选择、模型建立方法、注意要点,以及肺缺血-再灌注损伤及肺免疫排斥反应的产生机制进行了分析总结。方法:以计算机为主检索中国知识资料总库、PubMed数据库1982年1月至2013年9月有关肺移植方面的文献。英文检索词为"Lung Transplantation,Animal models,Reperfusion Injury";中文检索词为"肺移植;动物模型;缺血-再灌注损伤"。排除标准重复及陈旧的文献,保留50篇进行分析。结果与结论:目前以同种异体肺移植动物实验多见且对临床最有意义,肺移植动物实验以单肺移植为主。常用的肺移植模型主要有鼠单肺原位移植模型、兔原位肺移植模型、犬/猪原位左肺移植、犬双肺序贯性肺移植、猪自体肺移植模型、兔肺缺血再灌注模型。猪因其解剖和生理与人类相似,正在成为大动物实验的首选。动物实验和临床研究显示肺移植肺缺血再灌注损伤表现为双相模式,肺缺血再灌注损伤的发生早期(灌注后24 h内)与供体有关,晚期则主要取决于受体情况,其病理生理贯穿于供肺的切取、保存、再灌注及术后管理的整个过程。免疫排斥反应是一个由受者识别供者细胞表面的组织相容性抗原引发的复杂免疫反应,活化的T淋巴细胞在器官移植免疫反应中起关键性作用。

BACKGROUND：Establishing an animal model of lung transplantation has operational significance to the development of clinical lung transplantation.OBJECTIVE：To analyze and summarize animal selection, model establishment method, points to note and mechanism of lung ischemia-reperfusion injury and pulmonary immune rejection in the establishment of animal models as preclinical research of lung transplantation. METHODS：A computer-based retrieval of CNKI and PubMed database from January 1982 to September 2013 was performed for literature related to lung transplantation. The key words were“lung transplantation, animal models, reperfusion injury”in English and Chinese, respectively. After eliminating duplicate and obsolete literature,50 articles were included for further analysis. RESULTS AND CONCLUSION：Currently, animal experiments about al ogeneic lung transplantation are common, which are of significance for clinical lung transplantation. Single lung transplantation is mainly seen in animal models. The commonly used lung transplantation models include single lung orthotopic murine model,＆amp;nbsp;rabbit orthotopic lung transplantation, canine and porcine orthotopic left lung transplantation, canine bilateral sequential lung pulmonary transplantation, autologous pig lung transplant model, rabbit lung ischemia-reperfusion model. Because the anatomical and physiological features are similar to humans, pigs are becoming the preferred choice for large animal experiments. Animal experiments and clinical studies have shown that lung ischemia-reperfusion injury in lung transplantation represents a biphasic pattern：early occurrence of lung ischemia-reperfusion injury （24 hours after infusion） is related to lung donors, and the late occurrence mainly depends on receptors. Its pathophysiology runs through the whole process of donor lung resection, preservation and reperfusion as wel as postoperative management. Immune rejection is a complex immune response induced by identifying the donor cellsurface histocompatibility antigen, and activated T lymphocytes play a crucial role in the immune response in organ transplantation.