The Influence Of Insulin-Like Growth Factor-I On The Regeneration Of The Injured Urethral Sphincter Muscle Of Female Rat

Objective: To evaluate the effect of a new method of urodynamics in the research of female rat stress urinary incontinence model and present the urodynamic characteristic of urethral sphincter dysfunction of rat.Method: Twelve female virgin SD rats were performed urethral sphincter muscle injury by simulating a birth trauma. They all underwent urodynamic examination before and after trauma 14 days with catheters inducted into rat bladder per urethra Cystometry,leak point pressure and static urethral pressure profile were recorded.Results: Ten rats underwent research successfully, The average quantity of maximum bladder volume (MBV),bladder voiding pressure (VP),abdomen pressure leak point pressure (ALPP),maximum urethra pressure (MUP) and maximum urethra closure pressure (MUCP) before injury were ( 0.88±0.46 ) ml,( 26.50±6.42 ) cmH₂O (1cmH₂O=0.098KPa),(25.65±5.47)cmH₂O,(14.80±2.78)cmH₂O and(13.10±2.60)cmH₂O, respectively; while these parameters were(1.47±0.69)ml,(17.10±6.74)cmH₂O,(15.55±5.24)cmH₂O,(12.10±3.07)cmH₂O and(10.60±3.20)cmH₂O after damage. Compared with those at baseline, the average quantity of MBV increased by (0.60±0.40)ml(P<0.01); bladder VP and ALPP were significantly decreased by (9.40±8.74)cmH₂O and (9.50±4.92)cmH₂O, respectively(P <0.05). MUP and MUCP were decreased by(2.70±3.37)cmH₂O and (2.50±2.59)cmH₂O,respectively(P <0.05). Conclusion: The establishment of animal model for SUI by simulating a birth trauma and the new method of urodynamic examination to evaluate urethral sphincter muscle will make contribution to experimental research of SUI. Objective: To investigate the expression of insulin - like growth factor-I,II( IGF-I,II) during regeneration following urethral sphincter muscle injury in female Sprague- Dawley (SD) rats. To evaluate the effect of periurethral injection of IGF-I on the expression of organic IGF-I,IGF-II mRNA and the change of morphological Characteristics of urethral sphincter muscle during repair and regeneration period.Methods: Female virgin SD rats were performed urethral sphincter muscle injury by simulating a birth trauma.â‘ Then the rats (n=25) were killed in different time (2,4,6,8,14day) and specimens were processed for reverse transcription (RT) and polymerase chain reaction (PCR). A control group (n=5) underwent the same procedurewithout intravaginal balloon inflation.â‘¡Then the rats (n=50) was divided randomly into 2 subgroups: 25 rats underwent periurethral injection of 1.0μg human IGF-I to the middle urethral muscle and the other 25 rats as control group underwent saline injection. Five rats in each group were killed at 2,4,6,8,14 day respectively and the whole urethra specimens were processed forRT-PCR. A control group (n=5) underwent the same procedur without intravaginal balloon inflation and injection.â‘¢Then the rats (n=20) was divided randomly into 2 subgroups: 20 rats underwent periurethral injection of 1.0μg human IGF-I to the middle urethral muscle and the other 20 rats as control group underwent saline injection. Four rats in each group were killed at 2,4,6,8,14 day respectively, the middle one third of the urethra specimens were harvested for step serial histological paraffin sections and used for Masson's trichrome staining. Pathological changes and the area percentage of the striated muscle, the smooth muscle and the dense connective tissue were assessed with computer- assisted image analysis system. A control group (n=4) underwent the same procedur without intravaginal balloon inflation and injection.Results:â‘ IGF - I mRNA increased at day 4,6,8,14 after urethral sphincter muscle injury, especially at day 8 (P<0.05);IGF-II mRNA increased at day 4,6,8 after urethral sphincter muscle injury, especially at day 6,8(P<0.05).â‘¡After IGF-I injection, the expression of IGF-I mRNA increased significantly at all time points, with a peak on day 8.Comparied with saline control group, the difference was significant on day 4,14(P<0.01), and day 8(P<0.05). No expression on day 2 was noted in saline control group.The expression of IGF-II mRNA in experiment group increased on day 4,6,8,14.Comparied with saline control group,the significant difference noted on day 4(P<0.01).No expression on day 14 was noted in saline control group.â‘¢After simulated birth injury, the microstructure of mid-urethra changed significantly, with extensive disruption of the striated muscle layer, significant decline in urethral wall musculature (both smooth and striated), irregular shape and collagen fibers hyperplasia obviously. Comparied with saline control group, the area percentage of the striated muscle and the smooth muscle increased significantly on day 8 and day 14(P<0.05) after IGF-I injection.Conclusion: IGF-I,II mRNA was expressed during regeneration following urethral sphincter muscle injury and related to the healing process. The expression of organic IGF-I and IGF-II mRNA was improved by periurethral injection of IGF-I during regeneration period following urethral sphincter muscle injury in female rat. The repair of impaired urethral spincter muscle was improved by periurethral injection of IGF-I during regeneration period following urethral sphincter muscle injury in female rat. Our findings suggest that IGF-I facilitates the regeneration of the urethral muscles and may play a role in treatment of stress urinary incontinence induced by urethral sphincter muscle dysfunction.