Abstract:

Abstract:Objective To investigate the effects of oxidative stress on the expressions of transforming growth factor-β1(TGF-β1) and transforming growth factor-β receptor Ⅰ (TGF-βRⅠ) in rat unilateral ureteral obstruction (UUO) models.
Methods Thirfty  Wistar rats were randomly assigned into three groups:SOR group (sham-operated group,n=7);UUO group (operation group,n=11);US group (spironolactone 50 mg•kg^-1•d^-1 by daily gastric gavage after UUO,n=12).All the rats were killed  14 d after surgery.Renal fibrosis was assessed by the determination of tissue hydroxyproline (HYP) content.Malondialdehyde (MDA),superoxide dismutase (SOD) as well as aldosterone (ALD) content were measured.Histological changes were observed by HE and Masson staining.Immunohistochemistry  was performed to detect    the expressions of TGF-β1 and TGF-βRⅠ.Western blotting was used the determine the expression of  TGF-βRⅠ protein.Results Compared with sham group,the ALD contents in plasma and kidney tissues in UUO group significantly increased(P<0.01);the HYP and MDA levels in kidney tissues were also significantly increased(P<0.01),the SOD level was decreased(P<0.01);the expression levels of TGF-β1 and TGF-βRⅠ in kidney tissues were markedly increased(P<0.05).Compared with UUO group,the ALD contents in plasma and kidney tissues in US group were significantly decreased(P<0.01),the HYP and MDA levels in kidney tissues were also significanlty decreased (P<0.05，P<0.01)，the SOD level was increased(P<0.05)，the expressions TGF-β1 and  TGF-βRⅠ  in kidney tissues were markedly decreased(P<0.05). Conclusion The renal tubulointerstitial fibrosis induced by UUO may be related to the elevation of aldosterone,the increased production of oxidative stress and downregulation of TGF-β1 and TGF-βRⅠ.Aldosterone receptor antagonist spironolactone can partly alleviate renal fibrosis.

Key words: spironolactone, ureteral obstruction, fibrosis;oxidative stress, transforming growth factor beta 1, receptor,transforming growth factor beta