Rapamycin has been reported to inhibit hepatic fibrosis, lung fibrosis, renal fibrosis and subglottic stenosis. Fibrosis is also involved in urethral stricture. Therefore we investigated the effect of rapamycin on the inhibition of urethral stricture formation in a rabbit model. Firstly, models of urethral stricture were successfully established by electrocoagulation of the bulbar urethra with adult New Zealand male rabbits. Forty-six model rabbits were randomly assigned to four groups: high dose rapamycin (RH, 1.0 mg/day), low dose rapamycin (RL, 0.1 mg/day), DMSO alone (DMSO, solvent control) and normal saline (NS). Urethral stricture was assessed by a retrograde urethrogram and video-urethroscopy. Urethra pathology was evaluated by H&E staining and Sirius Red staining. After 28 days treatment, lumen reduction in the RH, RL, DMSO, and NS groups were 36.0%, 56.5%, 69.1%, and 82.9%, respectively. Comparison of the rapamycin groups (RH and RL) and control groups (DMSO and NS) indicated significantly less restriction in the rapamycin groups. Histopathology confirmed the presence of fibroblasts and an increase in collagen at the stricture site in the two control groups, but not in the RH or RL groups. These results indicate that rapamycin inhibits experimentally induced urethral stricture formation in rabbits. This may be due to its inhibition of fibroblast proliferation and collagen expression.
- Received January 5, 2011.
- Revision received April 1, 2011.
- Accepted April 1, 2011.
- The American Society for Pharmacology and Experimental Therapeutics