Triptolide attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction

Nephrology (Carlton). 2011 Feb;16(2):200-10. doi: 10.1111/j.1440-1797.2010.01359.x.

Abstract

Aim: Extracts of Tripterygium wilfordii Hook F. have been used to treat glomerulonephritis for more than 30 years in China. Most of the anti-inflammatory and immunosuppressive activities of these extracts can be attributed to triptolide (Trip). The present study was to investigate the effect of Trip on renal interstitial fibrosis in a model of unilateral ureteral obstruction (UUO).

Methods: UUO or sham-operated rats were randomly assigned to receive mycophenolate mofetil (MMF), Trip or vehicle and were killed on days 7 and 14 after UUO or sham operation. Kidney specimens were fixed for immunohistochemistry for myofibroblasts (α-smooth muscle actin, α-SMA), macrophages (ED-1), monocyte chemoattractant protein-1 (MCP-1) and osteopontin. Interstitial collagen deposition and amounts of transforming growth factor-β1 (TGF-β1) were determined by Sirius red staining and enzyme-linked immunosorbent assay, respectively. The mRNA expression of TGF-β1, connective tissue growth factor (CTGF), MCP-1 and osteopontin were measured by real-time polymerase chain reaction analysis.

Results: The scores for the density of α-SMA- and ED-1-positive cells, the staining of MCP-1 and osteopontin, interstitial collagen deposition and amounts of TGF-β1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF-β1, CTGF, MCP-1 and osteopontin.

Conclusion: Trip significantly attenuated tubulointerstitial fibrosis in a rat UUO model and the effect of Trip on renal fibrosis was similar to that of MMF. Trip may be useful as a potential candidate in the treatment of renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Analysis of Variance
  • Animals
  • Chemokine CCL2 / metabolism
  • Collagen / drug effects
  • Connective Tissue Growth Factor / metabolism
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Epoxy Compounds / pharmacology
  • Epoxy Compounds / therapeutic use
  • Fibrosis / etiology
  • Fibrosis / prevention & control
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / metabolism
  • Kidney / pathology*
  • Macrophage Activation / drug effects
  • Male
  • Osteopontin / metabolism
  • Phenanthrenes / pharmacology
  • Phenanthrenes / therapeutic use*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / metabolism
  • Ureteral Obstruction / complications*

Substances

  • Actins
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Diterpenes
  • Epoxy Compounds
  • Immunosuppressive Agents
  • Phenanthrenes
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Osteopontin
  • Connective Tissue Growth Factor
  • triptolide
  • Collagen