冷缺血会加剧大鼠肾移植中同种异体介导的损伤。

Cold ischemia augments allogeneic-mediated injury in rat kidney allografts.

作者信息

Kouwenhoven E A, de Bruin R W, Bajema I M, Marquet R L, Ijzermans J N

机构信息

Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Kidney Int. 2001 Mar;59(3):1142-8. doi: 10.1046/j.1523-1755.2001.0590031142.x.

DOI:10.1046/j.1523-1755.2001.0590031142.x

PMID:11231372

Abstract

BACKGROUND

Some clinical studies demonstrate that kidney grafts with prolonged cold ischemia experience early acute rejection more often than those with minimal ischemia. The mechanism, however, is putative. Therefore, the aim of this study was to unravel the impact of ischemia on the immune response in rat kidney allografts compared with that in isografts.

METHODS

To induce ischemic injury, donor kidneys were preserved for 24 hours in 4 degrees C University of Wisconsin solution before transplantation. No immunosuppression was administered. The histomorphology according to the BANFF criteria for acute rejection and infiltrating cells were assessed at days 1, 2, 3, 4, 6, and 8 post-transplantation.

RESULTS

In allografts, exposure of the kidney to ischemia led to a significantly earlier onset of interstitial cell infiltration and tubulitis compared with nonischemic allografts. The BANFF score of interstitial cell infiltration was 1 +/- 0 vs. 0.25 +/- 0.29 at day 3 and 2 +/- 0 vs. 1.25 +/- 0.25 at day 4. In contrast, in isografts, the effect of ischemia on the histology was not significant. From day 6, the histologic differences between ischemic and nonischemic grafts disappeared. Ischemia led to a more intense expression of P-selectin (day 1), intercellular adhesion molecule-1 (ICAM-1; day 2), and major histocompatibility complex (MHC) class II on endothelium and proximal tubular cells (day 2) in both allografts and isografts. Concurrently with the up-regulated ICAM-1 and MHC expression, significantly more CD4(+) cells and macrophages infiltrated the ischemic allografts at days 2 and 3 and the ischemic isografts at day 4. Importantly, the influx of these cells after ischemia was significantly greater in allografts than in isografts.

CONCLUSIONS

Cold ischemia augments allogeneic-mediated cell infiltration in rat kidney allografts. The earlier onset of acute rejection in 24-hour cold preserved allografts may be prevented by better preservation or treatment using tailored immunosuppression.

摘要

背景

一些临床研究表明，冷缺血时间延长的肾移植受者比冷缺血时间极短的受者更常发生早期急性排斥反应。然而，其机制尚不确定。因此，本研究旨在阐明与同基因移植相比，缺血对大鼠肾移植免疫反应的影响。

方法

为诱导缺血损伤，供肾在移植前于4℃威斯康星大学溶液中保存24小时。未给予免疫抑制。在移植后第1、2、3、4、6和8天，根据急性排斥反应的班夫标准评估组织形态学和浸润细胞。

结果

在同种异体移植中，与非缺血性同种异体移植相比，肾脏暴露于缺血导致间质细胞浸润和肾小管炎的发病时间显著提前。间质细胞浸润的班夫评分在移植后第3天为1±0，而非缺血性同种异体移植为0.25±0.29；在第4天分别为2±0和1.25±0.25。相比之下，在同基因移植中，缺血对组织学的影响不显著。从第6天开始，缺血性和非缺血性移植之间的组织学差异消失。缺血导致同种异体移植和同基因移植的内皮细胞和近端肾小管细胞上P-选择素（第1天）、细胞间黏附分子-1（ICAM-1；第2天）和主要组织相容性复合体（MHC）II类的表达更强烈（第2天）。与ICAM-1和MHC表达上调同时，在第2和3天，更多的CD4(+)细胞和巨噬细胞浸润缺血性同种异体移植，在第4天浸润缺血性同基因移植。重要的是，缺血后这些细胞的流入在同种异体移植中比在同基因移植中显著更大。