The Additional Detrimental Effects of Cold Preservation on Transplantation-Associated Injury in Kidneys from Living and Brain-Dead Donor Rats
The Additional Detrimental Effects of Cold Preservation on Transplantation-Associated Injury in Kidneys from Living and Brain-Dead Donor Rats
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DOI：
10.1097/tp.0b013e318191b2ca
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发表时间：
2009-01-15
期刊：
影响因子：
6.2
通讯作者：
Yard, Benito A.
中科院分区：
文献类型：
--
作者：
Hoeger, Simone;Petrov, Kiril;Yard, Benito A.
背景。脑死亡和低温保存是影响移植结果的主要异体抗原非依赖性危险因素。本研究旨在评估这些因素单独或联合对移植相关损伤的影响。F344大鼠脑死亡。6小时后取肾，在单侧切除的Lewis受体中直接移植，或在植入前在威斯康星大学溶液中低温保存24小时。从活体供体大鼠获得的同种异体移植物也进行冷藏或不冷藏。植入前通过末端脱氧核苷酸转移酶介导的dUTP镍端标记染色评估DNA损伤。移植后10天，按Banff '97分级进行肾脏组织学检查。定量聚合酶链反应分析细胞因子和粘附分子的表达。低温保存显著增加了移植肾中末端脱氧核苷酸转移酶介导的dUTP镍端标记阳性细胞的数量。移植后10天，组织学显示，当移植物被冷藏时，小管炎和血管炎评分较高。当从脑死亡（BD）供体获得移植物时，血管炎加重。BD与乳头状坏死相关，而非单纯低温保存。这在低温保存后更为常见。免疫组织学显示冷保存后MHC II+类细胞增多。BD联合冷保存显示VEGF和IL-10的表达程度较高。本研究强调脑死亡供体肾移植时应限制冷缺血时间。
Background. Brain death and cold preservation are major alloantigen-independent risk factors for transplantation Outcome. The present study was conducted to assess the influence of these factors on transplantation-associated injury independently or in combination.Methods. Brain death was induced in F344 rats. Renal grafts were harvested after 6 hr and either directly transplanted in unilateral nephrectomized Lewis recipient or Subjected to 24 hr of cold preservation in University of Wisconsin solution before implantation. Allografts obtained from living donor rats were also subjected to cold preservation or not. DNA damage was assessed before implantation by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining. Ten days after transplantation, renal histology was performed according to Banff '97 classification. The expressions of cytokines and adhesion molecules were analyzed by quantitative polymerase chain reaction.Results. Cold preservation significantly increased the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling positive cells in renal allografts. Ten days after transplantation, histology revealed a higher degree of tubulitis and vasculitis scores when the grafts were Subjected to cold storage. Vasculitis was aggravated when the graft was obtained from brain death (BD) donors. BD, but not cold preservation alone, was associated with papillary necrosis. This was more frequently observed after cold preservation. Immunohistology showed an increase in MHC class II+ cells after cold preservation. The combination of BD and cold preservation revealed a higher degree of VEGF and IL-10 expression.Conclusions. Our Study emphasizes that cold ischemia time should be limited when renal allografts from brain-dead donors are transplanted.