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

1)三种不同频率膀胱内电刺激阈值的测定显示，间质性膀胱炎(IC)患者对C纤维传入的刺激阈值明显低于良性前列腺增生症患者。2)对5例逼尿肌过度活动(DO)患者和6例保守治疗无效的间质性膀胱炎(IC)患者进行了白藜芦醇(RTX)膀胱内灌注治疗的临床和尿动力学研究。5例DO患者中有4例在滴注后1周内起效，起效时间3~9个月。6例IC患者中有5例在治疗后1周内储尿症状改善，膀胱疼痛评分和平均排尿量明显改善。然而，这些影响在1-2个月内消失。没有不良事件的报道。3)在大鼠，膀胱内注射三磷酸腺苷，一种P2X3受体激动剂，降低了膀胱c-…排尿能力和排尿阈值压力增加，这与初级膀胱传入的抗RTX C纤维传入活动增加有关。这些结果表明，P2X3受体的激活促进了大鼠膀胱中抗RTX的C纤维的形成。4)使用人羊膜(HAM)进行大鼠膀胱扩张术后，术后3个月内移植物中的尿路上皮、逼尿肌和神经纤维再生。HAM增强的膀胱具有足够的容量和顺应性，表明人羊膜可以作为膀胱增强的支架。我们还发现，骨髓来源的细胞在裸鼠体内移植到冷冻损伤的尿囊中后，可以分化为平滑肌细胞并重建平滑肌层。5)综上所述，本研究结果表明，各种针对膀胱上皮传入神经传导系统的药物以及利用人羊膜和骨髓来源的细胞的组织工程技术都可以治疗膀胱功能障碍。较少

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