Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism

Abstract

To investigate the effects of hydrogen sulfide (H2S) on renal fibrosis in diabetic rats and explore its mechanism. Male Sprague-Dawley rats were randomly divided into normal control (NC) group, a diabetic control (DC) group, diabetes mellitus (DM)+sodium hydrosulfide (NaHS) group and DM+DL-propargylglycine (PAG) group, with 8 rats in each group.Type 1 diabetes was induced in the respective groups by a single intraperitoneal (i.p.) injection of streptozotocin.From the fifth week, rats in the DM+NaHS and DM+PAG groups were injected (i.p.) with 56 μmol/kg NaHS and 40 mg/kg PAG once a day, respectively.After treatment for 4 weeks, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected.The deposition of renal collagen fibers was observed by Masson staining, and collagen volume fraction (CVF) was calculated.The ultrastructural change of renal tissue was observed by transmission electron microscopy.The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hydroxyproline (Hyp) in renal tissues were detected using the kits.The expression levels of TGF-β1, Smad3, phosphorylated (p)-Smad3 and collagen-IV (col-IV) in renal tissues were detected using Western blot. Compared with the NC group, the levels of FBG, BUN, SCr, CVF, IL-1β, IL-6, TNF-α and Hyp were increased; the deposition of renal collagen fibers and the ultrastructural damage were aggravated; the levels of TGF-β1, Smad3, p-Smad3, p-Smad3/Smad3 and col-IV were increased in the DC group.Compared with the DC group, excluding FBG, the aforementioned indices were improved in the DM+NaHS group; the aforementioned indices were further aggravated in the DM+PAG group. H2S attenuated renal fibrosis in diabetic rats, and the mechanism might be associated with the reduction of the release of proinflammatory cytokines, downregulation of the TGF-β1/Smad3 pathway, and inhibition of excessive accumulation of col-IV.