Department of Surgery, University of Groningen, Hanzeplein 1, Groningen, The Netherlands.
J Transl Med. 2013 Jan 29;11:22. doi: 10.1186/1479-5876-11-22.
Kidneys derived from brain dead donors have lower graft survival and higher graft-function loss compared to their living donor counterpart. Heat Shock Proteins (HSP) are a large family of stress proteins involved in maintaining cell homeostasis. We studied the role of stress-inducible genes Heme Oxygenase-1 (HO-1), HSP27, HSP40, and HSP70 in the kidney following a 4 hour period of brain death.
Brain death was induced in rats (n=6) by inflating a balloon catheter in the epidural space. Kidneys were analysed for HSPs using RT-PCR, Western blotting, and immunohistochemistry.
RT-PCR data showed a significant increase in gene expression for HO-1 and HSP70 in kidneys of brain dead rats. Western blotting revealed a massive increase in HO-1 protein in brain dead rat kidneys. Immunohistochemistry confirmed these findings, showing extensive HO-1 protein expression in the renal cortical tubules of brain dead rats. HSP70 protein was predominantly increased in renal distal tubules of brain dead rats treated for hypotension.
Renal stress caused by brain death induces expression of the cytoprotective genes HO-1 and HSP70, but not of HSP27 and HSP40. The upregulation of these cytoprotective genes indicate that renal damage occurs during brain death, and could be part of a protective or recuperative mechanism induced by brain death-associated stress.
与活体供体肾脏相比，来源于脑死亡供体的肾脏移植物的存活率较低，移植物功能丧失率较高。热休克蛋白（HSP）是一组参与维持细胞内环境稳定的应激蛋白。我们研究了脑死亡 4 小时后应激诱导基因血红素加氧酶-1（HO-1）、HSP27、HSP40 和 HSP70 在肾脏中的作用。
通过在硬膜外空间中充气气囊导管，在大鼠中诱导脑死亡（n=6）。使用 RT-PCR、Western blot 和免疫组织化学分析 HSPs。
RT-PCR 数据显示，脑死亡大鼠肾脏中 HO-1 和 HSP70 的基因表达显著增加。Western blot 显示脑死亡大鼠肾脏中 HO-1 蛋白大量增加。免疫组织化学证实了这些发现，显示脑死亡大鼠肾皮质小管中广泛存在 HO-1 蛋白表达。HSP70 蛋白主要在低血压治疗的脑死亡大鼠的肾远端小管中增加。
脑死亡引起的肾脏应激诱导保护性基因 HO-1 和 HSP70 的表达，但不诱导 HSP27 和 HSP40 的表达。这些保护性基因的上调表明，脑死亡期间发生了肾损伤，这可能是脑死亡相关应激诱导的保护性或恢复性机制的一部分。
