Bos E M, Schuurs T A, Kraan M, Ottens P J, van den Eijnden M M E D, Leuvenink H G D, Kampinga H H, van Goor H, Ploeg R J
University Hospital Groningen, Groningen 9700 RB, Netherlands.
Transplant Proc. 2005 Jan-Feb;37(1):359-60. doi: 10.1016/j.transproceed.2004.12.236.
The majority of transplanted kidneys are derived from brain-dead patients. This nonphysiological state influences the hemodynamic and hormonal status of the donor. As a result, kidneys derived from brain-dead donors have inferior graft survival and increased graft function loss. Heat shock proteins (HSPs) are a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. We studied renal expression of the genes HO-1, HSP27, HSP40, and HSP70 after experimental brain death in rats. Brain death was induced in male F344 rats by slowly inflating a balloon catheter in the epidural space. Untreated rats were used as controls. Animals were humanely killed after 4 hours of brain death. Kidneys were analysed using RT-PCR, Western blotting, and immunohistochemistry. RT-PCR showed an increase in expression of genes coding for HO-1 (3.6-fold; P < .05) and HSP70 (2.7-fold; P < .05) after brain death. Western blotting also revealed an increase in HO-1 protein levels (4.6-fold; P < .001) but changes in HSP70 protein expression were not detected. Immunohistochemistry showed increments of HO-1 protein expression in the renal cortical tubules of brain-dead rats. HSP70 was predominantly increased in renal distal tubules of brain-dead rats treated for hypotension. No changes were observed in renal HSP27 and HSP40 expression after brain death. Renal stress caused by brain death induces expression of the cytoprotective genes HO-1 and HSP70, but not of HSP27 and HSP40. The up-regulation of these cytoprotective genes could be part of a recuperative mechanism induced by stress associated with brain death.
大多数移植肾来自脑死亡患者。这种非生理状态会影响供体的血流动力学和激素状态。因此，来自脑死亡供体的肾脏移植存活率较低，移植肾功能丧失增加。热休克蛋白（HSPs）是一类应激诱导蛋白，参与维持细胞稳态和调节免疫系统。我们研究了大鼠实验性脑死亡后肾脏中HO-1、HSP27、HSP40和HSP70基因的表达。通过在硬膜外间隙缓慢充气球囊导管诱导雄性F344大鼠脑死亡。未处理的大鼠用作对照。脑死亡4小时后对动物实施安乐死。使用逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫组织化学分析肾脏。RT-PCR显示脑死亡后编码HO-1（3.6倍；P < 0.05）和HSP70（2.7倍；P < 0.05）的基因表达增加。蛋白质免疫印迹法也显示HO-1蛋白水平增加（4.6倍；P < 0.001），但未检测到HSP70蛋白表达的变化。免疫组织化学显示脑死亡大鼠肾皮质小管中HO-1蛋白表达增加。在接受低血压治疗的脑死亡大鼠的肾远端小管中，HSP70主要增加。脑死亡后未观察到肾脏HSP27和HSP40表达的变化。脑死亡引起的肾脏应激诱导细胞保护基因HO-1和HSP70的表达，但不诱导HSP27和HSP40的表达。这些细胞保护基因的上调可能是脑死亡相关应激诱导的恢复机制的一部分。
