RESUMEN
OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on expression of proinflammatory related gene and proteins of mitogen-activated protein kinase (MAPK) in renal tissues in ischemic/reperfusion (I/R) injury in mice. METHODS: Fifty male BABL/c mice were randomly divided into sham operation group (n=8), model group (n=10), and EP treatment group (n=32). EP treatment group was subdivided into EP pretreatment group (administration of 40 mg/kg EP 30 minutes before reproduction of model, n=8), and 4, 6 and 12 hours treatment groups (administration of 40 mg/kg EP 4, 6 and 12 hours after reproduction of model, respectively, n=8 in each group). Bilateral renal artery was occluded with a microvascular clamp for 30 minutes to reproduce kidney I/R injury model, and the kidney was harvested at 24 hours after I/R. The mRNA expressions of interleukins (IL-1ß, IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and high-mobility group box 1 (HMGB1) were determined by real time reverse transcription-polymerase chain reaction (RT-PCR). The changes in protein levels of MAPKs [extracellular regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38MAPK] were determined by Western blotting analysis. RESULTS: Real-time PCR assay showed that the mRNA expressions of IL-1ß, IL-6, TNF-α, ICAM-1, HMGB1 in renal tissue were much higher than those in sham operation group (IL-1ß: 12.05±8.08 vs. 3.18±1.13, IL-6: 10.26±6.85 vs. 0.81±0.34, TNF-α: 5.83±3.85 vs. 0.67±0.34, ICAM-1: 3.87±2.02 vs. 0.29±0.13, HMGB1: 652.82±78.50 vs. 112.31±32.50, all P<0.05); and the expression in EP treatment groups was markedly down-regulated than that in model group, especially in 12-hour treatment group (0.45±0.26, 0.66±0.13, 0.21±0.11, 0.05±0.02, 212.26±3.20, respectively, all P<0.05). Western blotting analysis revealed that the expression of the phosphorylated forms of ERK1/2, JNK, p38MAPK proteins was significantly higher than in sham operation group (p-ERK1/2: 1.13±0.38 vs. 0.48±0.34, p-JNK: 1.40±0.15 vs. 0.36±0.15, p-p38MAPK: 0.47±0.15 vs. 0.21±0.17, all P<0.05); the expression of the phosphorylated forms of ERK1/2, JNK, p38MAPK in each EP treatment group was significantly down-regulated compared with that in model group (all P<0.05). CONCLUSION: EP can effectively protect kidney from acute injury produced by I/R, which may be related to the regulation of proinflammatory genes and the MAPKs in renal tissue.