Saat Tanja C, Susa Denis, Roest Henk P, Kok Niels F M, van den Engel Sandra, Ijzermans Jan N M, de Bruin Ron W F
Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands.
Transplantation. 2014 Jul 15;98(1):15-21. doi: 10.1097/TP.0000000000000136.
The superior long-term survival of kidneys from living donors (LDs) compared with kidneys from donation-after-brain-death (DBD) and donation-after-cardiac-death (DCD) donors is now well established. However, comparative studies on transcriptional changes that occur at organ retrieval and during and after cold ischemia (CI) are sparse.
Using a rat model, we used qRT-PCR to examine expression levels of inflammatory, cytoprotective, and injury genes at different time points after organ retrieval. Cleaved caspase-3 was used to evaluate early apoptosis in DCD and DBD kidneys.
Immediately after retrieval, we found massive up-regulation of proinflammatory genes interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, P-selectin, and E-selectin in DBD compared with LD and DCD kidneys. A significant increase in the expression of injury markers Kim-1, p21, and the cytoprotective gene heme oxygenase-1 accompanied this. Bax was increased in DCD kidneys, and Bcl-2 was decreased in DBD kidneys. After 2 hr of CI in the LD group and 18 hr in the DBD and DCD groups, gene expression levels were similar to those found after retrieval. During 18 hr of cold storage, expression levels of these genes did not change. In DCD and DBD kidneys, early apoptosis increased after CI.
DISCUSSION/CONCLUSION: The gene expression profile in DBD kidneys represents an inflammatory and injury response to brain death. In contrast, DCD kidneys show only mild up-regulation of inflammatory and injury genes. These results may imply why delayed graft function in DCD kidneys does not have the deleterious effect it has on DBD kidneys.
与脑死亡后捐赠（DBD）和心脏死亡后捐赠（DCD）供体的肾脏相比，活体供体（LD）肾脏具有卓越的长期存活率，这一点现已得到充分证实。然而，关于器官获取时以及冷缺血（CI）期间和之后发生的转录变化的比较研究却很稀少。
利用大鼠模型，我们采用定量逆转录聚合酶链反应（qRT-PCR）检测器官获取后不同时间点炎症、细胞保护和损伤基因的表达水平。使用裂解的半胱天冬酶-3评估DCD和DBD肾脏中的早期凋亡。
获取后即刻，我们发现与LD和DCD肾脏相比，DBD肾脏中促炎基因白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、单核细胞趋化蛋白-1、P-选择素和E-选择素大量上调。损伤标志物Kim-1、p21以及细胞保护基因血红素加氧酶-1的表达也随之显著增加。DCD肾脏中Bax增加，而DBD肾脏中Bcl-2减少。LD组冷缺血2小时以及DBD和DCD组冷缺血18小时后，基因表达水平与获取后相似。在18小时冷保存期间，这些基因的表达水平没有变化。在DCD和DBD肾脏中，冷缺血后早期凋亡增加。
讨论/结论：DBD肾脏中的基因表达谱代表了对脑死亡的炎症和损伤反应。相比之下，DCD肾脏仅显示炎症和损伤基因的轻度上调。这些结果可能暗示了为什么DCD肾脏的延迟移植功能对其没有像对DBD肾脏那样的有害影响。
