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Hydrogen sulfide reduced renal tissue fibrosis by regulating autophagy in diabetic rats
1Department of Cardiology, The First Affiliated Hospital of South China University, Hengyang, Hunan 421001, P.R. China.
Abstract:
The present study aimed to explore the effect of hydrogen sulfide (H2S) on renal tissue fibrosis and its mechanism in diabetic rats. Rats were randomly divided into four groups (n=13/group): Control group; induced diabetes mellitus group (STZ); induced diabetes mellitus treated with H2S group (STZ + H2S); normal rats treated with H2S group (H2S). The diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg body weight streptozotocin (STZ); the control group was treated with saline every day (i.p); NaHS (100 µmol/kg i.p.) was administered to rats of STZ + H2S group and H2S group. After 8 weeks, rat body weight and 24 h proteinuria levels were determined in each group, renal pathological morphology was analyzed by Masson's trichrome staining, collagen IV content was detected by immunohistochemistry, and periodic acid‑Schiff (PAS) staining was performed on renal glomerular and tubular basement membranes. The expression levels of matrix metalloproteinase 9 (MMP9), MMP7, tissue inhibitor of metalloproteinase 1 (TIMP1), superoxide dismutase (SOD), serine/threonine kinase AKT, transforming growth factor (TGF)‑β1, nuclear factor (NF)‑κB and several autophagy related proteins were assessed by western blot analysis. Compared with the control group, renal tissue fibrosis was observed, collagen IV expression and the 24 h proteinuria quantity was markedly increased and the amount of PAS positive material in renal glomerular and tubular basement membranes was notably increased in STZ‑treated rats. Furthermore, the expression levels of MMP9, MMP7, TIMP1, autophagy‑associated proteins, AKT, TGF‑β1 and NF‑κB protein were significantly increased, and SOD expression levels were significantly decreased in the STZ group compared with the control (P<0.05). In the H2S+STZ group, renal tissue fibrosis and the expression of collagen IV were improved, 24 h proteinuria was decreased, the amount of PAS positive material in renal glomerular and tubular basement membranes was decreased, the expression levels MMP9, MMP7, TIMP1, autophagy‑associated proteins, AKT, TGF‑β1 and NF‑κB protein were significantly decreased, and the expression levels of SOD were significantly increased compared with the STZ group (P<0.05). In conclusion, H2S may improve renal tissue fibrosis by inhibiting autophagy, upregulating SOD and downregulating AKT, TGF‑β1 and NF-κB.
Insights
Hydrogen sulfide (H2S) treatment improved renal tissue fibrosis in diabetic rats by modulating key molecular pathways. This study highlights H2S as a potential therapeutic agent for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Diabetic nephropathy is a major complication of diabetes mellitus, characterized by renal tissue fibrosis.
- Hydrogen sulfide (H2S) has shown potential protective effects in various disease models.
Purpose of the Study:
- To investigate the therapeutic effect of hydrogen sulfide (H2S) on renal tissue fibrosis in streptozotocin (STZ)-induced diabetic rats.
- To elucidate the underlying mechanisms of H2S action in diabetic nephropathy.
Main Methods:
- Diabetic rat model induced by STZ injection.
- Treatment groups included control, STZ, STZ + H2S, and H2S alone.
- Assessment of renal fibrosis markers (Masson's trichrome, collagen IV, PAS staining).
- Western blot analysis for MMP9, MMP7, TIMP1, SOD, AKT, TGF-β1, NF-κB, and autophagy proteins.
Main Results:
- STZ-induced diabetes caused significant renal fibrosis, increased collagen IV and PAS staining, and elevated proteinuria.
- Diabetic rats showed increased expression of MMP9, MMP7, TIMP1, autophagy proteins, AKT, TGF-β1, and NF-κB, with decreased SOD.
- H2S treatment ameliorated renal fibrosis, reduced proteinuria, decreased collagen IV and PAS staining.
- H2S treatment normalized the expression of MMPs, TIMP1, autophagy proteins, AKT, TGF-β1, NF-κB, and increased SOD levels.
Conclusions:
- Hydrogen sulfide (H2S) demonstrates a protective effect against renal tissue fibrosis in diabetic rats.
- H2S may exert its renoprotective effects by inhibiting autophagy, upregulating superoxide dismutase (SOD), and downregulating AKT, transforming growth factor-β1 (TGF-β1), and nuclear factor-κB (NF-κB).
- H2S represents a promising therapeutic strategy for managing diabetic nephropathy.
