Takahashi Satoru, Chen Qin, Ogushi Tetsuo, Fujimura Tetsuya, Kumagai Jimpei, Matsumoto Shinya, Hijikata Shigeki, Tabata Yasuhiko, Kitamura Tadaichi
Department of Urology, Tokyo University Graduate School of Medicine, Japan.
J Urol. 2006 Aug;176(2):819-23. doi: 10.1016/j.juro.2006.03.070.
We evaluated the effects of sustained release basic fibroblast growth factor injection in rat urethra denervated by botulinum-A toxin (Wako Life Science, Osaka, Japan).
A total of 30 female Sprague-Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce chemical denervation of the urethral sphincter. Leak point pressure in the waking state was determined and a significant decrease in leak point pressure vs that in control rats was confirmed (mean +/- SD 58.7 +/- 6.2 vs 120.7 +/- 13.0 cm H(2)O, p <0.0001). Two weeks later 0, 50 and 200 microg basic fibroblast growth factor incorporating 200 microl gelatin hydrogels in 10 rats each were injected into the urethral sphincter, enabling sustained release of basic fibroblast growth factor for 2 weeks. Four weeks later injection leak point pressure measurement and histological evaluation of the urethra were performed.
Leak point pressure in rats with 50 and 200 microg basic fibroblast growth factor injection was significantly higher than in rats with the 0 microg injection (82.7 +/- 9.0 vs 95.1 +/- 6.2 and 119.3 +/- 8.1 cm H(2)O, p = 0.0021 and <0.0001, respectively). Maximum cross-sectional area of the urethral smooth muscle layer in the 50 and 200 microg groups significantly increased compared with that in the urethra in the 0 micro group, which was considered 100% (114.1% +/- 15.8% and 132.5% +/- 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross-sectional area of the striated sphincter in the 50 and 200 microg groups was greater than the 100% in the 0 microg group (112.3% +/- 15.6% and 124.3% +/- 14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri-atrophic zone in the 50 and 200 microg groups was significantly higher than in the 0 microg group (p = 0.027 and <0.0001, respectively).
Sustained release basic fibroblast growth factor injection in the chemically denervated urethral sphincter facilitates regeneration of the urethral muscles and improves sphincteric contractility. Endoscopic periurethral injection of basic fibroblast growth factor incorporating gelatin hydrogels may be an attractive therapy for stress urinary incontinence.
我们评估了在经肉毒杆菌A毒素（日本大阪和光纯药工业株式会社）去神经支配的大鼠尿道中注射缓释碱性成纤维细胞生长因子的效果。
总共30只雌性斯普拉格-道利大鼠接受尿道周围注射10 U肉毒杆菌A毒素，以诱导尿道括约肌化学去神经支配。测定清醒状态下的漏点压力，并确认与对照大鼠相比漏点压力显著降低（平均值±标准差分别为58.7±6.2和120.7±13.0 cm H₂O，p<0.0001）。两周后，将分别含有0、50和200 μg碱性成纤维细胞生长因子并与200 μl明胶水凝胶混合的溶液注射到每组10只大鼠的尿道括约肌中，使碱性成纤维细胞生长因子能够持续释放2周。四周后进行注射漏点压力测量和尿道组织学评估。
注射50和200 μg碱性成纤维细胞生长因子的大鼠的漏点压力显著高于注射0 μg的大鼠（分别为82.7±9.0 vs 95.1±6.2和119.3±8.1 cm H₂O，p分别为0.0021和<0.0001）。50和200 μg组尿道平滑肌层的最大横截面积与0 μg组相比显著增加，0 μg组被视为100%（分别为114.1%±15.8%和132.5%±13.4%，p分别为0.029和<0.0001）。同样，50和200 μg组横纹括约肌的横截面积大于0 μg组的100%（分别为112.3%±15.6%和124.3%±14.1%，p分别为0.069和0.0007）。50和200 μg组尿道萎缩周围区域的血管密度显著高于0 μg组（p分别为0.027和<0.0001）。
在化学去神经支配的尿道括约肌中注射缓释碱性成纤维细胞生长因子有助于尿道肌肉再生并改善括约肌收缩力。内镜下尿道周围注射含明胶水凝胶的碱性成纤维细胞生长因子可能是治疗压力性尿失禁的一种有吸引力的疗法。
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