PMID- 21272133 OWN - NLM STAT- MEDLINE DCOM- 20110607 LR - 20121115 IS - 1440-1797 (Electronic) IS - 1320-5358 (Linking) VI - 16 IP - 2 DP - 2011 Feb TI - Triptolide attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction. PG - 200-10 LID - 10.1111/j.1440-1797.2010.01359.x [doi] AB - 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 (alpha-smooth muscle actin, alpha-SMA), macrophages (ED-1), monocyte chemoattractant protein-1 (MCP-1) and osteopontin. Interstitial collagen deposition and amounts of transforming growth factor-beta1 (TGF-beta1) were determined by Sirius red staining and enzyme-linked immunosorbent assay, respectively. The mRNA expression of TGF-beta1, 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 alpha-SMA- and ED-1-positive cells, the staining of MCP-1 and osteopontin, interstitial collagen deposition and amounts of TGF-beta1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF-beta1, 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. CI - (c) 2010 The Authors. Nephrology (c) 2010 Asian Pacific Society of Nephrology. FAU - Yuan, Xiao-Peng AU - Yuan XP AD - Organ Transplant Centre, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - He, Xiao-Shun AU - He XS FAU - Wang, Chang-Xi AU - Wang CX FAU - Liu, Long-Shan AU - Liu LS FAU - Fu, Qian AU - Fu Q LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Australia TA - Nephrology (Carlton) JT - Nephrology (Carlton, Vic.) JID - 9615568 RN - 0 (Actins) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Diterpenes) RN - 0 (Epoxy Compounds) RN - 0 (Immunosuppressive Agents) RN - 0 (Phenanthrenes) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta1) RN - 0 (smooth muscle actin, rat) RN - 106441-73-0 (Osteopontin) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - 19ALD1S53J (triptolide) RN - 9007-34-5 (Collagen) SB - IM MH - Actins/metabolism MH - Analysis of Variance MH - Animals MH - Chemokine CCL2/metabolism MH - Collagen/drug effects MH - Connective Tissue Growth Factor/metabolism MH - Diterpenes/pharmacology/*therapeutic use MH - Epoxy Compounds/pharmacology/therapeutic use MH - Fibrosis/etiology/prevention & control MH - Immunosuppressive Agents/*therapeutic use MH - Kidney/metabolism/*pathology MH - Macrophage Activation/drug effects MH - Male MH - Osteopontin/metabolism MH - Phenanthrenes/pharmacology/*therapeutic use MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Transforming Growth Factor beta1/metabolism MH - Ureteral Obstruction/*complications EDAT- 2011/01/29 06:00 MHDA- 2011/06/08 06:00 CRDT- 2011/01/29 06:00 PHST- 2011/01/29 06:00 [entrez] PHST- 2011/01/29 06:00 [pubmed] PHST- 2011/06/08 06:00 [medline] AID - 10.1111/j.1440-1797.2010.01359.x [doi] PST - ppublish SO - Nephrology (Carlton). 2011 Feb;16(2):200-10. doi: 10.1111/j.1440-1797.2010.01359.x.