Hydrogen sulfide reduced renal tissue fibrosis by regulating autophagy in diabetic rats

作者：Li, Lin; Xiao, Ting; Li, Fang; Li, Yan; Zeng, Ou; Liu, Maojun; Liang, Biao; Li, Zining; Chu, Chun; Yang, Jun^*

来源：Molecular Medicine Reports, 2017, 16(2): 1715-1722.

DOI：10.3892/mmr.2017.6813

• diabetic nephropathy
• hydrogen sulfide
• autophagy
• superoxide dismutase
• AKT serine/threonine kinase
• transforming growth factor-beta 1
• nuclear factor-kappa B

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 mu mol/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) -beta 1, nuclear factor (NF)-kappa B 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-beta 1 and NF-kappa B 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-beta 1 and NF-kappa B 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-beta 1 and NF-kappa B.

• 出版日期2017-8