Urology · 2015
Collagenase Clostridium histolyticum (Xiaflex) for the Treatment of Urethral Stricture Disease in a Rat Model of Urethral Fibrosis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sangkum Premsant, Yafi Faysal A, Kim Hogyoung, Bouljihad Mostafa, Ranjan Manish, Datta Amrita, Mandava Sree Harsha, Sikka Suresh C, Abdel-Mageed Asim B, Moparty Krishnarao, Hellstrom Wayne J G
Аннотация
OBJECTIVE: To evaluate the treatment effect of collagenase Clostridium histolyticum (CCH) in a rat model of urethral fibrosis.
MATERIALS AND METHODS: Thirty male Sprague-Dawley rats (300-350 g) were divided into 5 groups. The rat urethra was injected with normal saline in the sham group and, in the other 4 groups, the rat urethra was injected with 10 μg of transforming growth factor beta 1 to create fibrosis of the urethra. Two weeks following transforming growth factor beta 1 injection, the rats were injected with varying doses of CCH or vehicles, depending on their group. The rats were then euthanized at 4 weeks after CCH or vehicle injection. Urethral tissue was harvested for histologic and molecular analyses. Type I and III collagen levels were evaluated by Western blot analysis.
RESULTS: There was urethral fibrosis and to significant increase in collagen type I and III expressions in the urethral fibrosis group compared with the sham group (P <.05). Urethral injection of CCH appeared to be safe and significantly reduce urethral fibrosis as well as collagen type I and III expressions in the high-dose CCH treatment groups when compared with the treatment control group (P <.01).
CONCLUSION: This study demonstrated a beneficial effect of CCH injections in a rat model of urethral fibrosis. These findings suggest a potential role for CCH as a therapeutic option in urethral stricture patients and warrant further investigation.
MATERIALS AND METHODS: Thirty male Sprague-Dawley rats (300-350 g) were divided into 5 groups. The rat urethra was injected with normal saline in the sham group and, in the other 4 groups, the rat urethra was injected with 10 μg of transforming growth factor beta 1 to create fibrosis of the urethra. Two weeks following transforming growth factor beta 1 injection, the rats were injected with varying doses of CCH or vehicles, depending on their group. The rats were then euthanized at 4 weeks after CCH or vehicle injection. Urethral tissue was harvested for histologic and molecular analyses. Type I and III collagen levels were evaluated by Western blot analysis.
RESULTS: There was urethral fibrosis and to significant increase in collagen type I and III expressions in the urethral fibrosis group compared with the sham group (P <.05). Urethral injection of CCH appeared to be safe and significantly reduce urethral fibrosis as well as collagen type I and III expressions in the high-dose CCH treatment groups when compared with the treatment control group (P <.01).
CONCLUSION: This study demonstrated a beneficial effect of CCH injections in a rat model of urethral fibrosis. These findings suggest a potential role for CCH as a therapeutic option in urethral stricture patients and warrant further investigation.