Polyethylene glycol reduces the inflammatory injury due to cold ischemia/reperfusion in autotransplanted pig kidneys
Polyethylene glycol reduces the inflammatory injury due to cold ischemia/reperfusion in autotransplanted pig kidneys
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DOI：
10.1046/j.1523-1755.2002.00473.x
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发表时间：
2002-08-01
影响因子：
19.6
通讯作者：
Vandewalle, A
中科院分区：
文献类型：
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作者：
Hauet, T;Goujon, JM;Vandewalle, A
背景。供体肾脏的储存条件可能影响缺血/再灌注损伤（IRI）对移植肾功能延迟恢复的有害后果。由于聚乙二醇（PEG）能够保护肾小管细胞免受冷损伤，我们测试了在冰冷的保存液中添加20kD的PEG对自体移植猪肾IRI的影响。
方法。将猪的左侧肾脏切除，用威斯康星大学（UW）溶液或含或不含30g/L PEG 20M的简化高钾或高钠溶液进行冷灌注，并在4℃下保存48小时。然后将肾脏自体移植，并切除对侧肾脏。随后进行肾脏活检，并在术后8至12周分析肾功能参数。
结果。在移植后第7天，用添加PEG的溶液进行冷灌注的肾脏比单独用UW溶液冷灌注的肾脏保存得更好，并且肾小管细胞核细胞损伤的迹象更不明显。PEG还几乎完全抑制了在用UW溶液冷灌注的肾脏的上皮小管细胞中检测到的主要组织相容性复合体II类的过度表达。PEG还显著减少了CD4⁺T淋巴细胞的数量，并限制了巨噬细胞/单核细胞的浸润以及移植后8 - 12周肾脏间质纤维化的进展。此外，用添加PEG的溶液灌注后自体移植的猪肾功能最佳，蛋白尿水平最低。
结论。这些发现表明，PEG抑制了IRI引起的早期炎症反应，改善了肾功能，并可能防止长期自体移植猪肾间质纤维化的进展。
Background. The conditions of storage of donor kidney may influence the deleterious consequences of ischemia/reperfusion injury (IRI) on delayed graft function. Since polyethylene glycol (PEG) can protect renal tubule cells against cold injury, we tested the effects of adding PEG 20 kD to ice-cold preservation solutions on the IRI of autotransplanted pig kidneys.Methods. The pigs' left kidneys were removed, cold-flushed with University of Wisconsin (UW) or simplified high K+ or high Na+ solutions with or without 30 g/L PEG 20M and stored for 48 hours at 4degreesC. The kidneys were then autotransplanted and the contralateral kidneys were removed. Kidney biopsies were then performed and renal function parameters were analyzed over 8 to 12 weeks following surgery.Results. The kidneys cold-flushed with PEG-supplemented solutions on day 7 post-transplantation were better preserved and exhibited less marked nuclear tubular cell damage than the kidneys cold-flushed with the UW solution alone. PEG also almost completely inhibited the overexpression of major histocompatibility complex class II that was detected in epithelial tubule cells from kidneys cold-flushed with the UW solution. PEG also significantly reduced the number of CD4(+) T lymphocytes and limited the infiltration of macrophages/monocytes and the progression of interstitial fibrosis in the 8- to 12-week post-transplanted kidneys. Moreover, pigs autotransplanted with kidneys flushed with PEG-supplemented solutions had the best renal function and the lowest levels of proteinuria.Conclusions. These findings indicate that PEG inhibits the early inflammatory response due to IRI, improves renal function, and may prevent the progression of interstitial fibrosis in the long-term autotransplanted pig kidney.