神經滋養因子以及細胞壓力受器在膀胱收縮力低下病患之尿路上皮表現量
張嘉峰  郭漢崇
花蓮慈濟醫院泌尿部
Stress receptor, neurotrophin and cell regeneration markers expression in the urothelium of detrusor overactivity, detrusor underactivity and detrusor hyperreflexia with inadequate contractility.
Jia Fong Jhang, Hann Chorng Kuo
Department of Urology, Hualein Tzu Chi Hospital

Purpose: The etiology of detrusor underactivity (DU) in patients without sacral spinal cord injury is still highly controversial. Previous study suggested the pathogenesis of DU and detrusor overactivity (DO) might be similar, and patients with DO may progress to detrusor hyperreflexia with inadequate contractility (DHIC) and DU with time. However, the mechanism is still unclear. The aim of current study is to investigate the role of stress receptors, neurotrophin and cell regeneration mark expression in the urothelium of patients with DO, DHIC and DU.

Materials and Methods: Patients with DO, DHIC and DU who were admitted for endoscopic surgery to relief bladder out resistance were enrolled into this study. The patients were asked to provide bladder specimens, and the specimens were taken by cold-cup bladder biopsy during the surgery under general anesthesia. The patients with spinal cord injury or concurrent acute bacterial cystitis were excluded in this study. The patients with stress urinary incontinence were also asked to provide bladder tissue during anti-incontinence surgery as control subjects. The patients were classified to patients with adequate bladder contractility (control and DO) and the patients with inadequate bladder contractility (DU+DHIC). The urodynamic parameters among these patients were recorded. The bladder specimens were investigated with western blot for the stress receptor corticotropin-releasing hormone receptor 1 and 2(CRHR1 and CRHR2), nerve growth factor, brain-derived neurotrophic factor (BDNF), and cell regeneration marker CD34.

Results: A total of 10 control subjects (59.6±10.8 years old), 19 patients with DO (71.0±11.5 years old), 7 DHIC (77.6±9.0 years old) and 13 DU (65.7±10.9 years old) were enrolled and provide bladder specimens. Among the 4 groups, the levels of NGF and CRFR1 expressions in urothelium were significantly higher in the control subjects. In comparison patients with adequate and inadequate bladder contractility, the NGF expression was higher in patients with adequate bladder contractility than that in the patients with inadequate bladder contractility. In compare DO patients to patients with inadequate bladder contractility, the NGF expression is higher and the CRFR2 expression is lower in the patients with DO. The NGF expression is significantly positively correlated to voiding detrusor pressure, and negatively correlated to residual urine volume and cystometeric bladder capacity. The CRFR1 expression was significantly positively correlated to maximal flow rate and voided volume. The CRFR2 was significantly positively correlated to first bladder filling sensation and first desire to voiding in the urodynamic study. Among all patients, age was not correlated to NGF, BDNF, CRFR1, CRFR2 and CD34 expression.

Conclusions: In compare to control subjects, patients with DO, DU and DHIC exhibit urothelial NGF and CRFR1 downregulation. NGF and CRFR1 expressions were correlated to urodynamic bladder contractility and empty function. Our results suggested NGF and CRFR1 downregulation may involve the pathogenesis of DO, DU and DHIC in patients without significant neurogenic injury