王脩仁、張嘉峰、郭漢崇

花蓮慈濟醫院 泌尿部

Hsiu-Jen Wang, Jia-Fong Jhang, Hann-Chorng Kuo

Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan  

 

Purpose: Ketamine cystitis(KC) is characterized by urinary frequency and bladder pain with history of ketamine abuse. Previous studies revealed nerve hyperplasia and fibrosis in the bladder of KC. However, the actual pathophysiology and the pathogenesis of these pathologic changes were 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 KC patients who were admitted to our hospital for treatment 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 KC patients were divided into two groups: mild KC and severe KC. The mild KC group means patient underwent only cystoscopic hydrodistention and the severe KC group means patients was treated with partial cystectomy with augmentation enterocystoplasty . Bladder specimens were taken during the procedures and were investigated for sensory receptors and related protein including with Western blotting and immunohistochemistry (IHC) of S-100 protein. 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) and Brain-derived Neurotrophic Factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) in these bladder specimens. The fibrogenic cystokine transforming growth factor beta (TGF-β) was also investigated. The Bladder specimens from patients with bladder cancer and underwent radical cystectomy were also obtained for western blotting and were considered as normal control(n=3).

Results: A total of 19 KC patients(mild:6 and severe:13) and 3 normal controls were enrolled. Three groups revealed difference in GAP43,TGF-β, TrK-A and BDNF and the similar outcomes revealed between normal and severe KC group. In compared with mild KC and severe KC, there were only TGF-β and TrK-A revealed statistical differences(table 1 and figure 1). In correlation analysis, there were significant differences between (1)GAP-43 and NGF, TrK-A, (2)TGF-β and TrK-A、TrK-B, (3)TrK-A and TrK-B and (4)TGF-β and CBC. The IHC of S-100 protein revealed 14/16 KC patients were S-100 positive.

Conclusions: Among the neurotrophin and its receptors we had investigated, GAP-43, TrK-A and BDNF were significantly higher in severe KC group. The TGF-beta was also higher in the severe KC bladder than that in mild KC and control. Trk-A, GAP-43, BDNF and TGF-beta may play an important role in the pathogenesis in KC, and may lead to disease progress to severe KC.