Objective:To investigate the activation of p38 signaling transduction cascade in renal ischemia reperfusion injury(IRI)and to study the effect of tempol,a free oxygen radical scavenger,on p38 activation.Methods:Male Sprague-Dawley rats were randomly divided into sham-operation group(n=10),IRI group(n=45)and IRI + tempol group(n=10).Animal IRI model was created by renal pedicle ligation(50 min)of the left kidney along with a contralateral nephrectomy followed by 2 h reperfusion.Rats were sacrificed on 0,5,10,15,30,45 min,1 and 2 h after renal reperfusion.Animals in IRI + tempol group were pretreated with tempol(100 mg/kg)1 h before undergoing the same protocol as in IRI group;the kidney was harvested after 45 min of reperfusion.Animals in the sham-operation group were subjected to contralateral nephrectomy without renal pedicle ligation and were sacrificed 45 min later.The renal p38 activities of the 3 groups were determined by Western blotting analysis.Malondialdehyde(MDA)content was detected and pro-inflammatory cytokine TNF-α,IL-1β levels were analyzed by ELISA.Results:Activation of p38 was observed in the kidney as early as 5 min after reperfusion and reached its peak 45 min after reperfusion and remained to be activated until 2 h after reperfusion(P0.05).The activities of renal p38 in IRI and IRI + tempol group were markedly increased compared with that of the sham-operation group(both P0.05).Pretreatment with tempol significantly inhibited IRI-induced p38 activation(P0.05);it also decreased MDA activity and TNF-α and IL-1β levels(both P0.05).Conclusion:Our results demonstrate that reactive oxygen species-mediated p38 activation plays an essential role in IRI-induced renal inflammatory damage in rats,suggesting that inhibition of p38 activation by tempol may be used for prophylaxis and treatment of IRI.