Effect of tempol, a free radical scavenger, on p38 activation in rats with renal ischemia reperfusion injury / 第二军医大学学报

ABSTRACT

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(P<0.05). The activities of renal p38 in IRI and IRI + tempol group were markedly increased compared with that of the sham-operation group(both P<0.05). Pretreatment with tempol significantly inhibited IRI-induced p38 activation(P<0.05); it also decreased MDA activity and TNF-α and IL-1β levels (both P<0.05). 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.