Dambros Miriam, Dambros Mara Celia, Lorenzetti Fabio, Dassen E L H M, van Koeveringe G A
Animal Research Center, School of Medicine Sao Leopoldo Mandic, SP, Brazil.
Department of Urology,University Hospital Maastricht, The Netherlands.
Int Braz J Urol. 2014 May-Jun;40(3):408-13. doi: 10.1590/S1677-5538.IBJU.2014.03.16.
Involuntary detrusor contractions play an important role in the development of urge incontinence. Also in an in-vitro situation contractions which develop spontaneously can be seen; a parallel with the in vivo observations is likely. In order to study this muscle overactivity we investigated the possibility to induce this phenomenon with oxidative stress using hypochlorous acid (HOCl).
Urinary bladder muscle strips from pigs were mounted in a custom made organ bath and incubated for 20 minutes in Krebs solution. Next HOCl (10 µM) was added to the organ bath and the onset of overactive contractions was closely followed. Overactivity was defined as a development of more than 5 phasic detrusor contractions per minute without any other provocation in the 30 minutes following addition of HOCl to the organ bath.
Of the 50 strips which were used 36 (72%) became overactive after exposure to HOCl during 30 minutes recording. In 76% of the overactive strips overactivity occurred within 5 minutes, in 19% between 5 and 15 minutes, and in 5% it took longer than 15 minutes. The overactivity could be stopped by washing out HOCl for 10 minutes after which still a significant contraction after EFS and ACh stimulation was seen.
It can be concluded that an oxidative stressor, like HOCl, is capable of inducing smooth muscle overactivity. This model can be used for the development and testing of new treatment modalities for the overactive detrusor. Furthermore, this study provides evidence for a causal relationship between oxidative stress and detrusor overactivity.
逼尿肌不自主收缩在急迫性尿失禁的发生中起重要作用。在体外情况下也能观察到自发产生的收缩；这可能与体内观察结果相似。为了研究这种肌肉过度活动，我们研究了使用次氯酸（HOCl）通过氧化应激诱导这种现象的可能性。
将猪的膀胱肌肉条安装在定制的器官浴中，并在 Krebs 溶液中孵育 20 分钟。接下来，将 HOCl（10 μM）添加到器官浴中，并密切观察过度活跃收缩的开始情况。过度活动定义为在向器官浴中添加 HOCl 后的 30 分钟内，每分钟出现超过 5 次相性逼尿肌收缩，且无任何其他刺激。
在使用的 50 条肌肉条中，有 36 条（72%）在 30 分钟记录期间暴露于 HOCl 后变得过度活跃。在 76%的过度活跃肌肉条中，过度活动在 5 分钟内出现，19%在 5 至 15 分钟之间出现，5%则需要超过 15 分钟。通过冲洗 HOCl 10 分钟可以停止过度活动，之后在电刺激和乙酰胆碱刺激后仍可见明显收缩。
可以得出结论，像 HOCl 这样的氧化应激源能够诱导平滑肌过度活动。该模型可用于开发和测试治疗逼尿肌过度活动的新治疗方法。此外，本研究为氧化应激与逼尿肌过度活动之间的因果关系提供了证据。
