Hauet Thierry, Han Zeqiu, Wang Yan, Hameury Frederic, Jayle Christophe, Gibelin Helene, Goujon Jean Michel, Eugene Michel, Papadopoulos Vassilios
Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, Surgères, France.
Transplantation. 2002 Dec 15;74(11):1507-15. doi: 10.1097/00007890-200212150-00006.
Ischemia-reperfusion injury is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria play a central role in this process.
Using an autotransplantation pig kidney model, both early (40 min and 7 days) and late (2-16 weeks) changes in renal function and morphology were determined after different periods of cold ischemia in University of Wisconsin or Euro-Collins solutions. We have also investigated the expression of the peripheral-type benzodiazepine receptor (PBR), which is also critical in maintaining outer mitochondrial membrane stability.
Function of the kidneys was better preserved after 1 hr and 24 hr than after 48 hr and 72 hr in Euro-Collins and University of Wisconsin solutions. Medulla injury was reduced in 1 hr-preserved and 24 hr-preserved groups. PBR was found to be present in epithelial cells of the deep cortical and outer medulla in both normal human and well-preserved pig kidneys. PBR expression was modulated by ischemia-reperfusion injury and the concurrent tubular injury and repair processes.
This study indicates that PBR expression correlates with the quality of kidney preservation and might serve as an index of kidney and mitochondria viability. Moreover, these data suggest that PBR might be involved in membrane biogenesis during reperfusion. In addition, considering the identical localization of PBR in human and pig kidneys, these findings could have a direct application in human clinical settings of kidney pathology.
缺血再灌注损伤与急性排斥反应、移植肾功能延迟恢复或慢性移植肾功能障碍风险增加相关。线粒体在此过程中起核心作用。
采用自体移植猪肾模型，在威斯康星大学溶液或欧洲柯林斯溶液中经历不同时长的冷缺血后，测定早期（40分钟和7天）和晚期（2 - 16周）的肾功能和形态变化。我们还研究了外周型苯二氮䓬受体（PBR）的表达，其在维持线粒体外膜稳定性方面也至关重要。
在欧洲柯林斯溶液和威斯康星大学溶液中，肾脏在保存1小时和24小时后的功能比保存48小时和72小时后的更好。在保存1小时和24小时的组中，髓质损伤减轻。在正常人和保存良好的猪肾中，均发现PBR存在于深层皮质和外髓质的上皮细胞中。PBR表达受缺血再灌注损伤以及同时发生的肾小管损伤和修复过程的调节。
本研究表明，PBR表达与肾脏保存质量相关，可能作为肾脏和线粒体活力的指标。此外，这些数据表明PBR可能参与再灌注期间的膜生物合成。此外，考虑到PBR在人和猪肾中的定位相同，这些发现可能直接应用于人类肾脏病理学临床环境。
