Chuang Yao-Chi, Chancellor Michael B, Seki Satoshi, Yoshimura Naoki, Tyagi Pradeep, Huang Leaf, Lavelle John P, De Groat William C, Fraser Matthew O
Division of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Urology. 2003 Mar;61(3):664-70. doi: 10.1016/s0090-4295(02)02280-x.
An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl).
Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments.
Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects.
Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.
通过膀胱内灌注硫酸鱼精蛋白（PS）（一种被认为会破坏尿路上皮屏障功能的物质）和生理浓度的氯化钾（KCl），建立大鼠膀胱过度活动症的急性动物模型。
对用乌拉坦麻醉的雌性大鼠进行连续膀胱测压（CMG），先以生理盐水（0.04 mL/分钟）充盈膀胱，随后膀胱内灌注由KCl（100或500 mM）或PS（10或30 mg/mL）组成的测试溶液60分钟。随后，对用10 mg/mL PS处理的动物膀胱内灌注100、300或500 mM KCl。一些动物在实验前4天用辣椒素（125 mg/kg皮下注射）进行预处理。
与单独使用KCl（100或500 mM）或低浓度PS（10 mg/mL）不同，膀胱内给予高浓度PS（30 mg/mL）会产生刺激作用，收缩间期缩短（缩短80.6%）。在灌注低浓度PS后，灌注300或500 mM KCl会产生刺激作用（收缩间期分别缩短76.9%或82.9%）。500 mM KCl灌注后刺激发作比300 mM KCl灌注后更快（10至15分钟比20至30分钟）。辣椒素预处理延迟了刺激发作（约60分钟）并减轻了刺激作用的程度（收缩间期缩短35.5%）。
PS处理后膀胱内给予KCl会激活辣椒素敏感传入神经和逼尿肌，可能还会激活辣椒素抵抗传入神经。对尿路上皮屏障功能适度的、无细胞毒性的刺激可导致显著的刺激反应。该模型可能有助于膀胱刺激和膀胱过度活动症的研究。
