神經滋養因子及組織纖維化因子在K他命膀胱炎中所扮演之角色

張嘉峰、郭漢崇

花蓮慈濟醫院 泌尿部

Jia-Fong Jhang, Hann-Chorng Kuo

Department of Urology, Haulien Tzu Chi Hospital.

 

Purpose: Previous studies revealed nerve hyperplasia and fibrosis in the bladder of ketamine related cystitis (KC). However, the pathogenesis of these pathologic changes was still unclear. The aim of current study is to investigate the neurotrophin expression and the fibrogenesis pathway in the KC urothelium.

Materials and Methods: The patients with KC who were admitted to our hospital for partial cystectomy with augmentation enterocystoplasty were enrolled into this study. The diagnosis of KC was based on previously recreational use of ketamine for at least 6 months and lower urinary tract symptoms. All patients underwent a comprehensive history review and urodynamic study. The bladder specimens was obtained from the surgery and sent to our laboratory for western blotting and immunochemical staining. Western blotting with quantification was used to investigate the expression of neurotrophin growth associated protein 43 (GAP-43), nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TrkA) in these bladder specimens. The fibrogenic cystokine transforming growth factor beta (TGF-β) was also investigated. Fluorescent immunochemical staining was also performed to verify the location of Trk-A and GAP-43 expression in the KC bladder. Bladder specimens from patients with bladder cancer and underwent radical cystectomy were also obtained for western blotting and were considered as normal control. Pearson’s correlation coefficients were calculated to determine the correlations between the quantification results of western blotting and clinical symptoms scores, including Visual Analogue Scale for pain (VAS), bladder capacity and compliance in the urodynamic study.

Results: A total of 13 KC patients and 3 normal controls were enrolled. The mean age in KC patients and controls is 29.0 ± 5.4 and 54.7± 10.5 years old, respectively. The western blotting quantification revealed significantly higher expression of neurotrophin GAP-43 and Trk-A in the KC bladder than that in the controls. The fibrogenic cytokine TGF-β also significantly increased in the KC bladder. The expression of GAP-43 in KC bladders was significantly correlated with TGF-β (r=0.714, p=0.001). The GAP-43 also was significantly correlated poor bladder compliance in urodynamic study (r=-0.548, p=0.022). The immunochemical staining also revealed GAP-43 and Trk-A expression in the KC bladder urothelium. Conclusions: Neurotrophin and fibrogenesis cytokines TGF-β might play an important role in the pathogenesis of KC. Increased neurotrophin expression was correlated with the upregulation of TGF-β, and may be associated with fbrogenesis in KC.