[Transfection of nuclear factor-kappaB decoy oligodeoxynucleotides prevents ischemic acute renal failure in rats].
OBJECTIVE
To investigate the effect of nuclear factor kappaB (NF-kappaB) decoy oligodeoxynucletides (ODN) on acute ischemic renal failure (iARF).


METHODS
The right kidney was resected and the left renal artery was isolated so as to establish the animal model of iARF in 18 SD rats. Then the 18 rats were divided into 3 groups of 6 rats to be infused into the left renal artery with protamine liposome (PL)-wrapped NF-kappaB decoy ODN (NF-kappaB group), scrambled ODN (scrambled group), or nothing (iARF group) and then underwent clamping of the left renal artery for 60 minutes. Another six rats underwent sham operation with infusion of normal saline and without clamping of the renal artery (sham group). Twenty-four hours later, blood was extracted from the inferior vena cava to detect the serum creatinine (Cr) and blood urine nitrogen (BUN). Normal saline was infused into the aorta to lavage the kidney. Then the kidney was taken to undergo histologic examination and examination of NF-kappaB/DNA binding activity, monocyte/macrophage (M/MPhi) infiltration and MCP-1 gene and protein expression.


RESULTS
In the rats injected with PL-wrapped NF-kappaB decoy ODN fluorescence was mainly distributed in the glomeruli 2 hours after injection of NF-kappaB decoy ODN, mainly in the renal tubules 12 hours later, and remarkably subsided after 24 hours. In the rats injected with un-wrapped NF-kappaB decoy ODN, no fluorescence was seen at any time point. After 24 h of reperfusion, compared with sham-operated animals, the serum Scr and BUN levels of the iARF group were about 10-times and 5 times those of the sham operation group (256 micromol/L +/- 84 micromol/L vs. 25 micromol/L +/- 5 micromol/L and 43 mmol/L +/- 13 mmol/L vs. 8.45 mmol/L +/- 1.07 mmol/L respectively. both P < 0.001), the NF-kappaB/DNA binding activity was markedly elevated [with the median values 1.75 vs. 0.15 relative density unit (RDU), P < 0.005], the renal tubular damage score was significantly higher (3.63 +/- 0.15 vs. 0.00 +/- 0.00 scores, P < 0.01), M/MPhi infiltration and the expression of MCP-1 gene were also increased. In comparison with the iARF group, the serum Cr level of the NF-kappaB decoy ODN treatment group was significantly lowered by 70% (79 micromol/L +/- 21 micromol/L vs. 256 micromol/L +/- 84 micromol/L, P < 0.01), the renal tubular damage score was markedly lower (1.85 +/- 0.15 vs. 3.63 +/- 0.15 scores, P < 0.01), and the M/MPhi infiltration and MCP-1 gene expression were inhibited.


CONCLUSIONS
NF-kappaB plays a critical role in renal ischemia/reperfusion injury and NF-kappaB decoy ODN reduces the renal dysfunction and injury associated with I/R of the kidney. In vivo transfection of NF-kappaB decoy ODN provides a novel therapeutic strategy for iARF.
Cao
Chang-chun
CC
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ding
Xiao-qiang
XQ
Ou
Zhou-luo
ZL
Liu
Chun-feng
CF
Li
Peng
P
Wang
Lei
L
Zhu
Chun-fang
CF
D058186:Acute Kidney Injury / Q000628:therapy*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000473:pathology; D009000:Monocytes / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014162:Transfection
D018932:Chemokine CCL2; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D004247:DNA