Atiemo Humphrey, Wynes Jacob, Chuo James, Nipkow Lisa, Sklar Geoffrey N, Chai Toby C
Division of Urology, University of Maryland, Baltimore, Maryland 21201, USA.
Urology. 2005 Mar;65(3):622-6. doi: 10.1016/j.urology.2004.10.057.
To assess the effects of intravesical injection of botulinum toxin type A (BTX) on a model of detrusor overactivity induced by intravesical infusions of adenosine triphosphate (ATP) and capsaicin. BTX has recently been used clinically to treat overactive bladder syndromes without a precise knowledge of the mechanism of action.
Twelve Sprague-Dawley rats underwent BTX injections. Six received 1.0 U and 6 received 0.5 U. BTX injections were done at bladder tube placement. Ten rats received saline injections as controls. After 48 hours of recovery, all 22 animals underwent awake, conscious cystometrography (CMG), performed using both saline and ATP (20 mM) intravesical infusion at 0.074 mL/min. In another 4 rats, capsaicin (100 microM) was infused intravesically before and after the BTX injections. The CMG parameters calculated included bladder contraction pressures and contraction frequencies (contractions per minute or Herz).
Intravesical saline CMG produced a contraction frequency of 0.78 +/- 0.10 Hz. Intravesical ATP doubled this voiding frequency to 1.45 +/- 0.18 Hz (P = 0.003). BTX treatment at 1.0 U reduced the frequency to 0.91 +/- 0.13 Hz (P = 0.02). BTX injection significantly decreased the bladder contraction pressure during saline and ATP CMG. However, 0.5 U BTX did not decrease ATP-induced overactivity; therefore, in the capsaicin experiments, 1.0 U BTX was used. Although BTX tended to reverse detrusor overactivity secondary to intravesical capsaicin, this difference was not statistically significant.
Intravesical infusion of either ATP or capsaicin can induce detrusor overactivity. BTX was more effective in blocking the effect of ATP than of capsaicin, although BTX injection did show a trend in reducing the contraction frequencies and amplitudes induced by capsaicin. The clinical utility of using BTX to treat overactive bladder syndromes and bladder hypersensory states, especially those that may be caused by an augmentation of the purinergic pathway, should be studied further.
评估膀胱内注射A型肉毒杆菌毒素（BTX）对膀胱内输注三磷酸腺苷（ATP）和辣椒素诱导的逼尿肌过度活动模型的影响。BTX最近已在临床上用于治疗膀胱过度活动综合征，但对其作用机制尚无确切了解。
12只Sprague-Dawley大鼠接受BTX注射。6只接受1.0单位，6只接受0.5单位。BTX在膀胱插管时注射。10只大鼠接受盐水注射作为对照。恢复48小时后，所有22只动物进行清醒状态下的膀胱测压（CMG），膀胱内以0.074 mL/min的速度输注盐水和ATP（20 mM）。另外4只大鼠在BTX注射前后膀胱内输注辣椒素（100 microM）。计算的CMG参数包括膀胱收缩压力和收缩频率（每分钟收缩次数或赫兹）。
膀胱内输注盐水时CMG的收缩频率为0.78±0.10赫兹。膀胱内输注ATP使排尿频率加倍至1.45±0.18赫兹（P = 0.003）。1.0单位的BTX治疗使频率降至0.91±0.13赫兹（P = 0.02）。BTX注射显著降低了盐水和ATP CMG期间的膀胱收缩压力。然而，0.5单位的BTX并未降低ATP诱导的过度活动；因此，在辣椒素实验中，使用了1.0单位的BTX。尽管BTX倾向于逆转膀胱内辣椒素引起的逼尿肌过度活动，但这种差异无统计学意义。
膀胱内输注ATP或辣椒素均可诱导逼尿肌过度活动。BTX在阻断ATP的作用方面比辣椒素更有效，尽管BTX注射确实显示出降低辣椒素诱导的收缩频率和幅度的趋势。使用BTX治疗膀胱过度活动综合征和膀胱感觉过敏状态，尤其是那些可能由嘌呤能途径增强引起的状态，其临床实用性应进一步研究。
