Improvements in early behavior of rat kidney allografts after treatment of the brain-dead donor
Improvements in early behavior of rat kidney allografts after treatment of the brain-dead donor
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DOI：
10.1097/00000658-200112000-00004
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发表时间：
2001-12-01
影响因子：
9
通讯作者：
Tilney, NL
中科院分区：
文献类型：
--
作者：
Pratschke, J;Kofla, G;Tilney, NL
目的探讨不同移植策略对未修饰宿主肾移植早期行为的影响，以提高脑死亡供体器官的质量。背景资料活体肾脏移植的效果始终优于尸体肾脏移植。作者最近表明，供体脑死亡会在数小时内引起外周器官的炎症变化，放大缺血再灌注损伤，加速急性和慢性排斥反应。迄今为止，通过供体激素治疗使移植物正常化尚未成功。方法采用标准化大鼠脑死亡模型。实验组包括活体和脑死亡供体的同种异体移植物受体（F344 -> LEW）。在诱导脑死亡后，供体立即接受静脉注射类固醇（阻断炎症细胞因子释放）或可溶性p -选择素糖蛋白配体（阻断初始选择素介导的细胞粘附）治疗。通过形态学、免疫组织学和逆转录-聚合酶链反应对移植肾进行连续10天的检查。结果未经修饰的脑死亡供者肾脏受者的总体存活率明显低于活体供者。接受了类固醇或sPSGL的脑死亡供体器官移植的动物比未接受治疗的脑死亡供体存活的时间要长得多。缺血再灌注损伤和急性排斥反应的强度降低。代表性促炎介质的细胞浸润和mRNA转录减少。结论脑死亡时器官供体的处理可显著改善肾移植后器官质量，使其达到活体供体的水平。
Objective To improve the quality of organs from brain-dead donors by assessing the influence of alternative strategies on the early behavior of kidneys after transplantation into unmodified hosts.Summary Background Data Kidneys transplanted from living donors perform consistently better than those from cadaver sources. The authors have recently shown that donor brain death produces inflammatory changes in peripheral organs within hours, amplifies coincident ischemia-reperfusion injury, and accelerates acute and chronic rejection. Normalization of the graft by donor hormone treatment has hitherto been unsuccessful.Methods A standardized rat model of brain death was used. Experimental groups included recipients of allogeneic grafts from living and brain-dead donors (F344 --> LEW). Donors were treated immediately after induction of brain death either with intravenous steroids, which block inflammatory cytokine release, or a soluble P-selectin glycoprotein ligand (sPSGL), which blocks initial selectin-mediated cellular adhesion. Kidney grafts were examined serially up to 10 days by morphology, immmunohistology, and reverse transcriptase-polymerase chain reaction.Results Overall survival of ummodified recipients of kidneys from brain-dead donors was significantly reduced versus living donors. Animals with organs from brain-dead donors that had received steroids or sPSGL survived significantly longer than those from untreated brain-dead donors. The intensity of ischemia-reperfusion injury and of acute rejection was reduced. Cellular infiltration and transcription of mRNA of representative proinflammatory mediators were diminished.Conclusions Treatment of organ donors at the time of brain death markedly improves organ quality after kidney transplantation, upgrading it to that from a living donor.