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- Title
Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction.
- Authors
Chun-feng Liu; Hong Liu; Yi Fang; Su-hua Jiang; Jia-ming Zhu; Xiao-qiang Ding
- Abstract
Purpose: The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot. Results: UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P<0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUOinduced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P<0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05). Conclusion: Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.
- Subjects
URETERIC obstruction; RAPAMYCIN; PATHOPHYSIOLOGY of anoxemia; INFLAMMATION treatment; RENAL fibrosis; LABORATORY rats
- Publication
Clinical & Investigative Medicine, 2014, Vol 37, Issue 3, pE142
- ISSN
0147-958X
- Publication type
Article
- DOI
10.25011/cim.v37i3.21381