The endogenous protection mechanism of lipoxin A4 in renal ischemia reperfusion injury in rats

Abstract

Objective To evaluate the relationship between Lipoxin A4 (LXA4) and the endogenous protection mechanism of acute kidney injury induced by renal ischemia reperfusion (I/R) injury in rats. Methods Twenty-four pathogen-free male SD rats were randomly divided into 4 groups (n=6 each): sham group, renal I/R injury group, LXA4 group and LXA4 receptor inhibitor Boc-2 group. Renal I/R injury model was established by excising the right kidney and transiently clamping the left renal artery. In sham group, only right kidney was removed. In I/R group, the right kidney was removed and the left renal artery was transiently clamped. In LXA4 group, LXA4 (200 μg/kg) was injected via the tail vein respectively at 36, 24 and 12 h before renal I/R. In Boc-2 group, Boc-2 (100 mg/kg) was injected via the tail vein respectively at 36, 24 and 12 h before renal I/R, and then LXA4 (200 μg/kg) was injected 6 h after each Boc-2 administration. At 24 h after reperfusion, the serum creatinine (Scr) and blood urea nitrogen (BUN), superoxide dismutase (SOD) and malondialdehyde (MDA) in the renal cortex were measured, and the expression of cleaved cysteinyl aspartate-specific protease (Caspase)-3, B cell lymphoma/leukemia-2 (bcl-2), mitofusin 2 (Mfn2), voltage dependent anion channel 1 (VDAC1) and cytochrome C was detected by Western blotting. Results Compared with sham group, Scr [(57.67±5.43) μmol/L], BUN [(18.16±2.61) mmol/L] and SOD [(6.06±1.13) U/mgprot] was increased (P=0.000), while MDA [(50.51±5.91) nmol/mgprot] was decreased (P=0.000) in renal cortex, expression of cleaved caspase-3 (1.80±0.19) and cytochrome C (1.55±0.28) was up-regulated (P=0.000), while expression of bcl-2 (0.70±0.07), Mfn2 (0.82±0.17)and VDAC1 (0.81±0.09) was down-regulated (P=0.000) in I/R group. Compared with I/R injury group, Scr [(39.01±4.81) μmol/L, P=0.000], BUN [(10.47±2.79) mmol/L, P=0.000] and SOD [(3.65±0.83) U/mgprot, P=0.003] was decreased, while MDA [(70.60±8.46) nmol/mgprot] was increased (P=0.000) in renal cortex, expression of cleaved caspase-3 (1.08±0.12, P=0.000) and cytochrome C (1.01±0.21, P=0.002) was down-regulated while expression of bcl-2 (1.21±0.12, P=0.000), Mfn2 (1.15±0.17, P=0.02) and VDAC1 (1.09±0.13, P=0.001) was up-regulated in group LXA4. Compared with group LXA4, Scr [(48.12±2.72)μmol/L, P=0.003], BUN [(15.10±2.30) mmol/L, P=0.004] and SOD [(5.30±0.97) U/mgprot, P=0.004] was increased, while MDA [(54.44±7.22) nmol/mgprot] was decreased (P=0.040) in renal cortex, expression of cleaved caspase-3 (1.64±0.21, P=0.000) and cytochrome C (1.43±0.26, P=0.014) was up-regulated, while expression of bcl-2 (0.80±0.07, P=0.000), Mfn2 (0.74±0.11, P=0.003) and VDAC1 (0.79±0.09, P=0.001) was down-regulated in Boc-2 group. Conclusion LXA4 in partially is involved in the endogenous protection mechanism of acute kidney injury induced by transiently renal I/R injury via inhibiting tubular cell apoptosis and mitochondrial damage in rats. Key words: Lipoxin A4; Renal ischemia; Reperfusion injury