[Change in plasma H2S level and therapeutic effect of H2S supplementation in tubulointerstitial fibrosis among rats with unilateral ureteral obstruction].

Abstract

OBJECTIVE:

To observe the level in plasma hydrogen sulfide (H2S) and the expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (two key synthetases for endogenous H2S generation in the kidney) in obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S in TIF.

METHODS:

Ninety-six male Sprague-Dawley rats were randomly divided into sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low-dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and 7.0 μmol/kg respectively) twice daily immediately after operation, and the sham-operated and model groups were intraperitoneally injected with an identical volume of normal saline. In each group, 8 rats were randomly selected and sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was measured by deproteinization. The obstructed kidney tissue was subjected to hematoxylin and eosin staining and Masson staining, and the renal tubulointerstitial injury was evaluated under a microscope. mRNA and protein expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR and immunohistochemistry respectively.

RESULTS:

The degree of UUO-induced renal tubulointerstitial injury was negatively correlated with plasma H2S concentration in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of TIF was reduced (P<0.01). There were no significant differences in plasma H2S level and mRNA and protein expression of CBS and CSE between the low-dose and high-dose NaHS groups (P>0.05).

CONCLUSIONS:

H2S is involved in the development of UUO-induced TIF, and the CBS/H2S and CSE/H2S systems play key roles in this process. H2S supplementation can delay the progression of TIF.

• Authors: De-An Zhao, Jun Liu, Qian Huang, Zi-Ming Han
• Journal: Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics (Zhongguo Dang Dai Er Ke Za Zhi) Vol. 15 Issue 10 Pg. 903-8 (Oct 2013) ISSN: 1008-8830 [Print] China
• PMID: 24131846 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Cystathionine beta-Synthase
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Cystathionine beta-Synthase (analysis, genetics)
• Cystathionine gamma-Lyase (analysis, genetics)
• Dietary Supplements
• Fibrosis
• Hydrogen Sulfide (administration & dosage, blood)
• Kidney Tubules (pathology)
• Male
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Ureteral Obstruction (blood, pathology)