Renal protection by delayed ischaemic preconditioning is associated with inhibition of the inflammatory response and NF‐<i>κ</i>B activation

Abstract

Brief and sublethal ischaemia renders an organ tolerant to subsequent prolonged ischaemia, which is called ischaemic preconditioning (IPC). In regard to the beneficial effects and endogenous mechanisms of renal delayed IPC, few data are available. In this study, we aim at determining reno-protective effects of delayed IPC against ischaemia-reperfusion (I/R) injury, and illustrating whether these effects are associated with suppressing inflammation and nuclear factor-kappaB (NF-kappaB) activation. I/R injury was induced by clamping both renal pedicles for 40 min, followed by 24 h of reperfusion. The rats were subjected to ischaemia for 20 min (preconditioning) or sham surgery (non- preconditioning) at day 4 before I/R. Functional and morphological parameters were evaluated at 24 h after reperfusion. At the same time, macrophage (ED-1(+)) infiltration, and the expression of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) were assessed by immunohistochemistry. Moreover, I kappa B-alpha degradation and NF-kappaB/DNA binding activity were analyzed. Compared with rats exposed to I/R injury, preconditioned rats had a significant decrease in levels of serum creatinine (Scr, 384.3 +/- 21.8 micromol/L vs. 52.5 +/- 21.7 micromol/L; p<0.001), blood urea nitrogen (BUN, 40.4 +/- 2.7 mmol/L vs. 15.9 +/- 4.2 mmol/L; p<0.001) and serum aspartate aminotransferase (AST, 486.7 +/- 58.6 IU/L vs. 267.3 +/- 43.9 IU/L; p<0.001). Parallel to the above changes, preconditioned rats preserved structural integrity and decreased tubulointerstitial damage scores (3.4 +/- 0.3 vs. 0.2 +/- 0.05; p<0.001) and ED-1(+) cell infiltration (25.3 +/- 3.5 vs. 6.2 +/- 1.2 cells/HPF, p<0.01). Furthermore, our results showed that the expression of ICAM-1 and TNF-alpha, the degree of I kappa B-alpha degradation, and NF-kappaB/DNA binding activity were reduced by IPC. Taken together, our results demonstrated that delayed IPC offered both functional and histological protection, which may be related to suppression of inflammation in preconditioned kidneys.