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心理应激引起的雌性小鼠膀胱过度活动与膀胱收缩力增强有关。

Bladder overactivity induced by psychological stress in female mice is associated with enhanced bladder contractility.

机构信息

Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.

Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.

出版信息

Life Sci. 2021 Jan 15;265:118735. doi: 10.1016/j.lfs.2020.118735. Epub 2020 Nov 7.

Abstract

AIMS

To investigates the effects of water avoidance stress on voiding behaviour and functional bladder responses in mice.

MAIN METHODS

Mice in the Stress group were exposed to water avoidance stress (WAS) for 1 h/day for 10 days, Controls were age-matched and housed normally. Voiding behaviour was measured periodically throughout the stress protocol and bladders were isolated 24-h after final stress exposure to measure bladder compliance, spontaneous phasic activity, contractile responses, and release of urothelial mediators.

KEY FINDINGS

Repeated stress exposure induced a significant increase in plasma corticosterone levels in the WAS group compared to control. An overactive bladder phenotype was observed in WAS mice, causing a significant increase in the number of voiding events observed from as early as day-3, and a 7-fold increase following 10-days' stress. This increase in voiding frequency was associated with a significant decrease in void size, an increase in the number of small voids, but no change in total voided volume. Bladders from stressed mice showed a significant increase in the maximum responses to the muscarinic agonist carbachol (p < 0.01), in addition to enhanced pressure responses to the purinergic agonists ATP (p < 0.05) and αβ-mATP (p < 0.05), and non-receptor mediated contractions to KCl (p < 0.05) compared to controls. Nerve-mediated bladder contractions to electric field stimulation were not significantly affected by stress, nor were spontaneous phasic contractions or release of urothelial ATP and acetylcholine.

SIGNIFICANCE

Repeated exposure to water avoidance stress produced an overactive bladder phenotype, confirmed by increased voiding frequency, and associated with enhanced bladder contractile responses.

摘要

目的

研究回避水应激对小鼠排尿行为和功能性膀胱反应的影响。

方法

应激组小鼠每天暴露于回避水应激(WAS)1 小时,共 10 天,对照组则进行年龄匹配并正常饲养。在应激方案期间定期测量排尿行为,最后一次应激暴露 24 小时后分离膀胱,以测量膀胱顺应性、自发性相位活动、收缩反应和尿路上皮介质的释放。

主要发现

与对照组相比,重复应激暴露导致 WAS 组血浆皮质酮水平显著升高。WAS 小鼠表现出过度活跃的膀胱表型,导致从第 3 天开始观察到的排尿次数显著增加,而在 10 天应激后增加了 7 倍。这种排尿频率的增加与排尿量显著减少、小尿次数增加但总排尿量不变有关。应激小鼠的膀胱对毒蕈碱激动剂 carbachol 的最大反应显著增加(p<0.01),此外,对嘌呤能激动剂 ATP(p<0.05)和 αβ-mATP(p<0.05)的压力反应以及对 KCl 的非受体介导收缩反应也显著增加(p<0.05),与对照组相比。应激对神经介导的膀胱收缩无显著影响,自发性相位收缩或尿路上皮 ATP 和乙酰胆碱的释放也不受影响。

意义

反复暴露于回避水应激会产生过度活跃的膀胱表型,这可通过增加排尿频率来证实,并与增强的膀胱收缩反应相关。

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