Development of new therapy for bladder dysfunction:Combined approaches of phamiacology and tissue engineering

1)三种不同频率膀胱内尿路上皮电刺激阈值测量显示，间质性膀胱炎（IC）患者的c纤维传入刺激阈值明显低于良性前列腺增生患者。2)对5例逼尿肌过度活跃（DO）患者和6例标准保守治疗无效的间质性膀胱炎（IC）患者膀胱内灌注树脂干扰素（RTX）的临床和尿动力学效果进行了观察。5例DO患者中有4例在注射后1周内出现缓解，疗效持续3-9个月。6例IC患者中有5例在治疗后1周内尿潴留症状得到改善，膀胱疼痛评分和平均排尿量均显著改善。然而，这些影响在1-2个月内消失。无不良事件报告。3)在大鼠中，膀胱内ATP（一种P2X3受体的激动剂）降低了膀胱c，增加了排尿的容量和阈压，这与原发性膀胱传入神经中rtx抗性c纤维传入活动的增加有关。这些结果表明，P2X3受体的激活促进了大鼠膀胱中rtx抗性c -纤维的形成。4)人羊膜（hAM）大鼠膀胱增强术后3个月内显示移植物尿路上皮、逼尿肌平滑肌和神经纤维再生。人工羊膜增强膀胱显示出足够的容量和顺应性，表明人羊膜可作为膀胱增强支架。我们还发现，在裸鼠体内，骨髓来源的细胞植入冻伤的膀胱后，可以分化为平滑肌细胞并重建平滑肌层。5)综上所述，目前的研究结果表明，膀胱功能障碍可以通过针对膀胱尿路上皮-传入神经传导系统的各种药物以及利用人羊膜和骨髓源性细胞的组织工程技术来治疗。少

1) The threshold measurement for intravesical urothelial electric stimulation with three different frequencies revealed that Patients with interstitial cystitis (IC) had significantly lower threshold for C-fiber afferents stimulation than those with benign prostatic hyperplasia.2) The clinical and urodynamic effects of intravesical instillation of resiniferatoxin (RTX) were investigated in 5 patients with detrusor overactivity (DO) and 6 patients with interstitial cystitis (IC) resistant against standard conservative therapy. Four of 5 DO patients responded to the treatment within 1 week after the instillation, and the effect lasted for 3-9 months. Five of 6 IC patients showed improvement of their storage symptoms within 1 week after the treatment, and bladder pain score and mean voided volume were significantly improved. However, these effects disappeared within 1-2 months. No adverse events were reported.3) In rats, intravesical ATP, an agonist for P2X3 receptors, decreased bladder c … More apacity and threshold pressure for voiding, which was associated with an increase in the afferent activity of RTX-resistant C-fibers of the primary bladder afferents. Theses results suggest that activation of P2X3 receptors facilitates RTX-resistant C-fibers in the rat bladder.4) Bladder augmentation in rats using human amniotic membrane (hAM) revealed regeneration of urothelium, detrusor smooth muscle, and nerve fibers in the graft within 3 months postoperatively. The hAM-augmented bladders displayed adequate capacity and compliance, indicating that human amniotic membrane can be used as a scaffold for bladder augmentation. We have also found that in nude mice, bone marrow-derived cells, when implanted into freeze-injured urinary bladders, can differentiate into smooth muscle cells and reconstruct smooth muscle layers.5) All together, the results of the present studies indicate that bladder dysfunction can be treated with various pharmacological agents targeting urothelial-afferent neurotransduction system of the bladder as well as tissue engineering techniques using human amniotic membrane and bone marrow-derived cells. Less