Postconditioning attenuates renal ischemia-reperfusion injury by preventing DAF down-regulation

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.