Effect of Novel Gasotransmitter hydrogen sulfide on renal fibrosis and connexins expression in diabetic rats

Abstract

To explore the effects of hydrogen sulfide (H2S) on renal fibrosis and the expressions of connexins and matrix metalloproteinase (MMP) in diabetic rats. Method: SD rats were divided into 4 groups randomly: control group(n = 12), STZ group (n = 12), STZ+ H2S group (n = 12), and H2S group (n = 12). Diabetic model was induced by intraperitoneal injections of STZ. After 72 h after injection, the rats whose blood glucose were higher than 16.7 mmol/L. STZ+H2S group and H2S group were injected NaHS by intraperitoneal. Control group and STZ group were injected with the same dose of normal saline (NS) in equal doses every day. 8 weeks later, urine were collected. The expression of connexin and matrix metalloproteinase was analyzed by Western blot. We measured the Kidney hydroxyproline content by hydrolysis method. Type II collagen content was detected by immunohistochemical method and Masson staining. Results: Compared with the control group, collagen accumulation was markedly enhanced, and the content of type II collagen, kidney hydroxyproline and timp-2 were boosted in STZ group mice (P < 0.01), while the expressions of CX40,CX43, CX45, MMP-1 and MMP-2 were obviously deceased (P < 0.01). Compared with STZ group, the expressions of CX40, CX43, CX45, MMP-1 and MMP-2 were significantly increased (P < 0.01), while the content of type II collagen, kidney hydroxyproline and timp-2 expression were markedly deceased in STZ+H2S group. Conclusion: H2S may attenuate renal fibrosis by up-regulating the expressions of CX40, CX43, CX45 and regulating the MMPs/TIMPs parameters.