Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions

Ren Fail. 2014 Mar;36(2):292-9. doi: 10.3109/0886022X.2013.844645. Epub 2013 Oct 24.

Abstract

Objective: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats.

Methods: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-β1, CTGF mRNA.

Results: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-β1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-β1, and FN proteins and the collagen thickness. The expression of TGF-β1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation.

Conclusion: Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-β1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.

MeSH terms

  • Animals
  • Connective Tissue Growth Factor / metabolism*
  • Cytokines / metabolism
  • Dialysis Solutions*
  • Fibronectins / metabolism
  • Glucose / administration & dosage*
  • Male
  • Peritoneal Dialysis*
  • Peritoneum / metabolism*
  • Peritoneum / pathology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation

Substances

  • Cytokines
  • Dialysis Solutions
  • Fibronectins
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • Glucose