Therapeutic effects of IGF-1 on stress urinary incontinence in rats with simulated childbirth trauma

Abstract

Purpose: We examined the effect of IGF-1 in a rat model of stress urinary incontinence induced by simulated childbirth trauma.

Materials and methods: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. Four, 7, 14 and 28 days after distension we performed functional assessment by measuring leak point pressure, urethral baseline pressure and the urethral response during a passive increment in intravesical pressure. The expression of IGF-1 and IGF1R mRNA and protein in damaged tissues was examined by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Thereafter hrIGF-1 (50 and 150 μg/kg per day) was continuously delivered from 1 day before distension using subcutaneous osmotic pumps. Four and 7 days after distension the effect of hrIGF-1 treatment was examined by functional analysis of leak point pressure, urethral baseline pressure and the urethral response as well as Western blot and histological analysis.

Results: After 4 and 7 days rats with vaginal distension had significantly decreased leak point pressure, urethral baseline pressure and urethral responses. IGF-1 and IGF1R mRNA and protein levels were significantly increased in urethral and pudendal nerves 4 and 7 days after distension. IGF-1 treated groups showed significant improvement in leak point pressure, urethral baseline pressure and urethral responses 4 and 7 days after distension. Moreover, IGF-1 treatment increased Akt phosphorylation and induced cellular proliferation and antiapoptotic effects in the urethra.

Conclusions: IGF-1 treatment accelerated recovery from stress urinary incontinence induced by simulated childbirth trauma in association with activation of the Akt signal transduction pathway in rats. This suggests that IGF-1 has therapeutic potential for stress urinary incontinence in women.

Keywords: ELISA; GAPDH; IGF-1; IGF-1 receptor; IGF1R; LPP; PBS; PCR; RT-PCR; SUI; UBP; VD; enzyme-linked immunosorbent assay; glyceraldehyde-3-phosphate dehydrogenase; hr; human recombinant; insulin-like growth factor 1; insulin-like growth factor-1; leak point pressure; parturition; phosphate buffered saline; polymerase chain reaction; reverse transcriptase-PCR; stress; stress urinary incontinence; urethra; urethral baseline pressure; urinary incontinence; vagina; vaginal distension.