Abstract: Objective To investigate the effects and possible mechanisms of spironolactone and valsartan on renal interstitial fibrosis of rat unilateral ureteral obstruction (UUO) model. Methods Fifty-one wistar rats were randomly assigned into five groups: SOR group (sham-operated group,n=7); UUO group (operation group ,n=11);UUO +SPI group (spironolactone 50mg/(kg·d) by daily gastric gavage after UUO, n=12); UUO+ARB group(valsartan 10mg/(kg·d) by daily gastric gavage after UUO, n=11) and UUO+SPI+ARB group(combined gastric gavage the same dose of spironolactone and valsartan after UUO, n=10). All the rats were killed at 14 days after surgery. Histological changes were observed by HE and Masson staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) content, renal tubular cell apoptosis, western blotting of cysteinyl aspartate specific proteinase-3(caspase-3) were measured. Results UUO induced a significant increase in MDA content, renal tubular cell apoptosis, western blotting of caspase-3 as well as severe morphology changes and a marked decrease in SOD content. However, three treatment groups ameliorated what had mentioned. Conclusions Spironolactone and valsartan significantly alleviate renal tubulointerstitial fibrosis and renal tubular cell apoptosis in obstructed kidney. Spironolactone and valsartan may markedly suppress the production of oxidative stress and the expression of caspase-3, which may be partly related to the caspase-dependent pathways.

Key words: Valsartan, Fibrosis, Oxidative stress, Caspase-3