Faure Jean Pierre, Hauet Thierry, Han Zeqiu, Goujon Jean Michel, Petit Isabelle, Mauco Gerard, Eugene Michel, Carretier Michel, Papadopoulos Vassilios
Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, Surgères, and Faculté de Médecine (EA 2426), Poitiers and Centre Hospitalier et Universitaire, Poitiers, France.
J Pharmacol Exp Ther. 2002 Sep;302(3):861-70. doi: 10.1124/jpet.102.033688.
Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4(+), PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.
移植后的缺血再灌注损伤（IRI）是导致移植肾功能延迟的主要原因，对移植肾的早期和晚期功能均有负面影响，并会加重急性排斥反应。我们之前已经表明，在离体灌注猪和大鼠肾脏模型中，聚乙二醇（PEG）尤其是PEG 20M对冷缺血和再灌注损伤具有保护作用。我们进一步拓展这些观察结果，研究在简化的保存液中添加不同剂量（30g或50g/l）的PEG（ICPEG30或ICPEG50）或不添加PEG（IC）对猪肾脏长时间冷保存（48小时）后减少IRI的作用，同时与欧洲柯林斯液和威斯康星大学液进行比较。采用生化方法和质子核磁共振波谱法对肾功能和髓质损伤进行研究。在再灌注后（30 - 40分钟）、第7天和第14天以及第4、8和12周进行组织学和炎症细胞研究。还对参与胆固醇稳态的线粒体蛋白外周型苯二氮䓬受体（PBR）进行了研究。结果表明，ICPEG30改善了肾功能并减少了髓质损伤。ICPEG30还改善了肾小管功能并强烈保护线粒体完整性。该组IRI后的炎症反应明显减轻，尤其是TCD4(+)淋巴细胞，PBR表达在早期和慢性功能障碍发展过程中受IRI影响。本研究清楚地表明PEG在肾脏保存中具有有益作用，并提示PBR作为IRI和修复过程标志物的作用。
