Ischemic preconditioning attenuates renal ischemia-reperfusion injury by inhibiting activation of IKKbeta and inflammatory response.
BACKGROUND
Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated as a key mediator of reperfusion injury. Activation of NF-kappaB is dependent upon the phosphorylation of its inhibitor, IkappaB, by the specific inhibitory kappaB kinase (IKK) subunit, IKKbeta. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKbeta. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-kappaB, we approached the relationship between NGAL and IKKbeta.


METHODS
Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKbeta in renal tissues.


RESULTS
Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 +/- 12.98 vs. 205.89 +/- 19.16 mircomol/l, p < 0.01; tubulointerstitial injury scores, 1.3 +/- 0.48 vs. 3.8 +/- 0.79, p < 0.01). In addition, expressions of IKKbeta (0.95 +/- 0.21 vs. 1.74 +/- 0.17, p < 0.05) and NGAL (1.71 +/- 0.032 vs. 2.66 +/- 0.078, p < 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKbeta and NGAL were in positive correlation (R = 0.965 > R(0.01)(30) = 0.448, p < 0.01).


CONCLUSIONS
The evidence suggests that IKKbeta may play a role in renal I/R injury and give rise to the generation of NGAL. It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKbeta may offer a clinically accessible target for preventing renal injury following I/R.
Chen
Xin
X
Department of Nephrology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Liu
Xiaodong
X
Wan
Xin
X
Wu
Yu
Y
Chen
Yu
Y
Cao
Changchun
C
D000818:Animals; D051550:I-kappa B Kinase / Q000502:physiology*; D007249:Inflammation / Q000517:prevention & control*; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D051550:I-kappa B Kinase