무엇이 방광섬유화를 일으키는가? : 비정상 신경분포 또는 비정상 방광역학의 영향

Abstract

Purpose: Bladder tissue fibrosis is characterized by the abnormal deposition of connective tissue within different layers of the bladder wall, resulting in "non-compliance". The different etiologies of bladder fibrosis are, either neurogenic, which encompasses myelodysplasia and spinal cord injury, or nonneurogenic, due to bladder outlet obstruction. In this study, we examined whether bladder fibrosis is due to the effect of abnormal innervation or to abnormal bladder dynamics. Materials and Methods: Thirty-five Sprague-Dawley male rats (250-300g) were divided into four groups; normal (n=5), bilateral pelvic nerve transection; denervation (n=10), vesicostomy (n=10), and vesicostomy after denervation (n=10) groups. After 4 weeks, the bladders of animals in each group were obtained. In the histologic study, the collagen to muscle ratio in Masson's trichrome stain and the elastin density (%) in Van Gieson stain were determined using a Metamorph ver 4.6r5 image analyzer. TGF-beta1 and collagen III protein expressions were detected by Western blotting. Results: The collagen to muscle ratios of the normal group, vesicostomy, denervation and vesicostomy after denervation group were; 0.67+/-0.04*, 0.67+/-0.04*, 1.25+/-0.03* and 0.96+/-0.02, respectively (*p>0.001), and the elastin densities were 14.73+/-1.09**, 16.38+/-2.27, 23.6+/-1.93** and 18.35+/-1.27, respectively (**p>0.01). By Western blotting, the denervation group showed significantly increased TGF-beta1 and collagen III protein expressions compared with the normal group and the vesicostomy group. Conclusions: The orders of the collagen to muscle ratio and of the deposition of elastin were; denervation > vesicostomy after denervation > vesicostomy > normal group by histologic study. The levels of TGF-beta1 and of collagen III in the denervation group were higher than in the vesicostomy after denervation group. The above findings show that both pressure and nerve innervation in the bladder, have significant effects on the process of bladder fibrosis. Meanwhile, vesicostomy could reduce the fibrotic effect caused by denervation, although it is not complete.