Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
J Urol. 2010 Jun;183(6):2424-31. doi: 10.1016/j.juro.2010.01.066. Epub 2010 Apr 18.
There is increasing evidence that ischemic postconditioning may noticeably attenuate renal ischemic-reperfusion injury, although the specific mechanisms are not fully clear. We examined the role of the complement system, especially membrane bound complement regulatory proteins, in postconditioning after renal ischemic-reperfusion injury in a right nephrectomy rat model.
After right nephrectomy the left renal pedicles were occluded for 60 minutes, followed by 24-hour reperfusion. Postconditioning was induced by 6 cycles of 10-second ischemia and 10-second reperfusion before reperfusion. After 24-hour reperfusion without a control blood samples were obtained via the vena cava. Renal samples were also obtained. DAF, CD46, CD59, C3aR and C5aR mRNA and protein expression was examined by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry. C3/C9 deposition in tissue was detected by immunofluorescence. Renal function, histology and cellular apoptosis were also observed.
In renal tissue postconditioning prevents DAF down-regulation, which is induced by ischemic-reperfusion injury. It results in the decreased renal necrosis caused by ischemic-reperfusion injury mediated complement activation. However, in all experimental groups renal CD46/CD59 expression was not altered. Increased DAF expression due to postconditioning may decrease C5aR expression in renal tissues compared with ischemic-reperfusion injury, which can decrease apoptosis. C3aR expression did not differ among the experimental groups.
These findings provide new evidence that postconditioning protects kidneys from ischemic-reperfusion injury, at least in part, by preventing DAF down-regulation.
越来越多的证据表明，缺血后处理可以明显减轻肾缺血再灌注损伤，尽管其具体机制尚不完全清楚。我们在右肾切除术大鼠模型中研究了补体系统，尤其是膜结合补体调节蛋白，在肾缺血再灌注损伤后处理中的作用。
右肾切除术后，左肾蒂夹闭 60 分钟，再灌注 24 小时。再灌注前，通过 6 个周期的 10 秒缺血和 10 秒再灌注来诱导后处理。再灌注 24 小时后，通过腔静脉采集对照血样。还采集了肾样。通过逆转录聚合酶链反应、Western blot 和免疫组织化学检测 DAF、CD46、CD59、C3aR 和 C5aR 的 mRNA 和蛋白表达。通过免疫荧光检测组织中 C3/C9 的沉积。还观察了肾功能、组织学和细胞凋亡。
在肾组织中，后处理可防止 DAF 下调，DAF 下调是由缺血再灌注损伤引起的。它导致缺血再灌注损伤介导的补体激活引起的肾坏死减少。然而，在所有实验组中，肾 CD46/CD59 的表达均未改变。后处理导致的 DAF 表达增加可能会降低肾组织中 C5aR 的表达，从而减少细胞凋亡。C3aR 的表达在实验组之间没有差异。
这些发现提供了新的证据，表明后处理通过防止 DAF 下调来保护肾脏免受缺血再灌注损伤，至少部分是这样。
