200單位肉毒桿菌素膀胱逼尿肌注射在慢性脊髓損傷病患可改善膀胱泌尿上皮功能缺損，但感覺蛋白質的表現無明顯改善
陳聖復1、張嘉慧1、郭漢崇1
1佛教花蓮慈濟綜合醫院泌尿部
Detrusor onabotulinumtoxinA 200u injection improved urothelial dysfunction but not altered urothelial sensory protein expressions in spinal cord injured patients
Sheng-Fu Chen1, Chia-Hwei Chang1, Hann-Chorng Kuo1
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University1
Purpose: OnabotulinumtoxinA detrusor injection effectively improves neurogenic detrusor overactivity (NDO) in patients with SCI in clinical low urinary tract symptoms and urodynamic parameters. The current study investigated changes in urothelial dysfunction and sensory protein expression in the bladder urothelium with time after a single onabotulinumtoxin injection in SCI patients.
Materials and Methods: A total of 26 patients with chronic SCI causing NDO and urinary incontinence were treated with a single injection of 200 U onabotulinumtoxinA to the detrusor muscle. Ten women with stress urinary incontinence but no overactive bladder symptom admitted for anti-incontinence surgery served as controls. Cold-cup biopsies were taken randomly at the posterior wall. Patients were followed up at VUDS and assessment of bladder and voiding conditions and satisfaction with treatment were performed 3 and 6 months after treatment. Bladder tissues were investigated for urothelial barrier and inflammation proteins by immunofluorescence quantification as well as sensory proteins by Western blotting.
Results: A total of 26 SCI patients (9 females; 17 males) and 10 controls (all females) were enrolled in the current study. After onabotulinumtoxionA injection, the bladder compliance and bladder capacity increased. Urothelial expression of E-cadherin was significantly lower, while mast cell activity and apoptotic cell count were significantly higher in SCI bladders compared to controls (Table 1). Increased E-cadherin and ZO-1(zonula occludens-1) levels were noted 3 months after injection but were reduced at 6 months. Mast and apoptotic cell TUNEL (tryptase and terminal deoxynucleotidyl transferase dUTP nick end-labeling )counts showed no change at 3 or 6 months after treatment. Among the urothelial sensory proteins, only baseline M3 and eNOS levels were significantly lower in SCI bladders versus controls. Interestingly, there were no significant changes in any of the sensory proteins examined from baseline to 3 or 6 months in SCI patients after onabotulinumtoxinA injection. (Table 1)
Conclusions: A single injection of 200 U onabotulinumtoxinA in SCI patients improved urothelial dysfunction in the expression of E-cadherin and ZO-1 at 3 months, but the effect declined 6 months after treatment. Urothelial sensory protein levels did not significantly change after onabotulinumtoxinA treatment. These results imply that the therapeutic effect of single 200 U onabotulinumtoxinA treatment might not be adequate for NDO