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手术植入膀胱导管对小鼠排尿功能的影响。

Impact of surgical bladder catheter implantation on voiding function in mice.

作者信息

Rubin Benjamin E, Vizzard Margaret A, Herrera Gerald M

机构信息

Larner College of Medicine, University of Vermont, Burlington, Vermont, United States.

Department of Neurological Sciences, University of Vermont, Burlington, Vermont, United States.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2025 Jun 1;328(6):R718-R726. doi: 10.1152/ajpregu.00300.2024. Epub 2025 May 7.

DOI:10.1152/ajpregu.00300.2024
PMID:40331573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145183/
Abstract

Lower urinary tract (LUT) disorders significantly impact quality of life, yet treatment advancements remain limited. Animal models, such as those using invasive urodynamics with surgically implanted suprapubic bladder catheters, are vital for preclinical research. However, the effects of catheter implantation on bladder function have not been well characterized. The primary objective of this study was to evaluate the impact of surgical bladder catheter implantation on voiding function in male and female mice by comparing noninvasive voiding behavior before and after bladder catheter implantation in the same animals. We assessed voiding parameters in 16 mice ( = 7 male and = 9 female) before and after catheter implantation using noninvasive voiding assays conducted in a home-cage environment. These assessments revealed significant changes in postimplantation voiding behavior, characterized by increased void frequency ( = 0.0004) and decreases in both void volumes ( < 0.0001) and intermicturition intervals ( = 0.0006). Urodynamic studies further demonstrated that bladder capacities were reduced 10%-30% compared with preimplantation estimates, reflecting physical reductions in bladder volume caused by the catheterization procedure. Similar results in the voiding function were seen in both male and female mice. These findings demonstrate that surgical catheter implantation alters voiding function, with overall consistent effects observed across sexes. The observed changes likely result from physical bladder size reduction due to catheter placement and the use of a purse-string suture to secure the catheter. This study underscores the importance of accounting for procedural artifacts in preclinical LUT research to ensure translational relevance. This study provides the first characterization of voiding behavior and bladder function changes following surgical bladder catheter implantation in mice, as measured using noninvasive assays. We show that surgical catheter implantation reduces bladder capacity and significantly alters voiding parameters, including frequency, volume, and intermicturition intervals, with overall consistent effects across sexes. These findings highlight the importance of accounting for procedural artifacts when interpreting LUT function in preclinical models, ensuring translational relevance for future studies.

摘要

下尿路(LUT)疾病对生活质量有显著影响,但治疗进展仍然有限。动物模型,如那些使用带有手术植入耻骨上膀胱导管的侵入性尿动力学的模型,对临床前研究至关重要。然而,导管植入对膀胱功能的影响尚未得到充分表征。本研究的主要目的是通过比较同一动物膀胱导管植入前后的非侵入性排尿行为,评估手术膀胱导管植入对雄性和雌性小鼠排尿功能的影响。我们在笼内环境中使用非侵入性排尿试验评估了16只小鼠(雄性7只,雌性9只)导管植入前后的排尿参数。这些评估揭示了植入后排尿行为的显著变化,其特征为排尿频率增加(P = 0.0004)、排尿量减少(P < 0.0001)和排尿间隔时间缩短(P = 约0.0006)。尿动力学研究进一步表明,与植入前估计相比,膀胱容量减少了10%-30%,反映了导尿过程导致的膀胱体积的实际减小。雄性和雌性小鼠在排尿功能方面都出现了类似结果。这些发现表明,手术导管植入会改变排尿功能,且在不同性别中观察到的总体影响一致。观察到的变化可能是由于导管放置导致膀胱实际尺寸减小以及使用荷包缝合来固定导管所致。本研究强调了在临床前LUT研究中考虑操作假象以确保转化相关性的重要性。本研究首次描述了小鼠手术膀胱导管植入后使用非侵入性试验测量的排尿行为和膀胱功能变化。我们表明,手术导管植入会降低膀胱容量并显著改变排尿参数,包括频率、量和排尿间隔时间,且在不同性别中总体影响一致。这些发现突出了在解释临床前模型中的LUT功能时考虑操作假象以确保未来研究的转化相关性的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/0c2d2ff1ec16/nihms-2083141-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/2680c31cb452/nihms-2083141-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/83a558d8aa4d/nihms-2083141-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/7268ed66adbb/nihms-2083141-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/0c2d2ff1ec16/nihms-2083141-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/2680c31cb452/nihms-2083141-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/83a558d8aa4d/nihms-2083141-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/7268ed66adbb/nihms-2083141-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed70/12145183/0c2d2ff1ec16/nihms-2083141-f0005.jpg

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本文引用的文献

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Lower Urinary Tract Symptoms in Depression: A Review.抑郁症中的下尿路症状:综述
Health Psychol Res. 2023 Jul 15;11:81040. doi: 10.52965/001c.81040. eCollection 2023.
2
Afferent nerve activity in a mouse model increases with faster bladder filling rates in vitro, but voiding behavior remains unaltered in vivo.在体外,小鼠模型中的传入神经活动随着更快的膀胱充盈率而增加,但在体内排尿行为保持不变。
Am J Physiol Regul Integr Comp Physiol. 2022 Nov 1;323(5):R682-R693. doi: 10.1152/ajpregu.00156.2022. Epub 2022 Sep 19.
3
Machine learning-assisted fluoroscopy of bladder function in awake mice.
机器学习辅助清醒小鼠膀胱功能透视检查。
Elife. 2022 Sep 6;11:e79378. doi: 10.7554/eLife.79378.
4
Prevalence, Burden, and Treatment of Lower Urinary Tract Symptoms in Men Aged 50 and Older: A Systematic Review of the Literature.50岁及以上男性下尿路症状的患病率、负担及治疗:文献系统评价
SAGE Open Nurs. 2018 Dec 26;4:2377960818811773. doi: 10.1177/2377960818811773. eCollection 2018 Jan-Dec.
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Best practices for cystometric evaluation of lower urinary tract function in muriform rodents.用于多态啮齿动物下尿路功能尿动力学评估的最佳实践。
Neurourol Urodyn. 2020 Aug;39(6):1868-1884. doi: 10.1002/nau.24415. Epub 2020 Jun 8.
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TRPV4 blockade reduces voiding frequency, ATP release, and pelvic sensitivity in mice with chronic urothelial overexpression of NGF.TRPV4 阻断减少了慢性尿路上皮过表达神经生长因子的小鼠的排尿频率、ATP 释放和盆底敏感性。
Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1695-F1706. doi: 10.1152/ajprenal.00147.2019. Epub 2019 Oct 21.
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Urodynamic measurements reflect physiological bladder function in rats.尿动力学测量反映了大鼠的膀胱生理功能。
Neurourol Urodyn. 2018 Apr;37(4):1266-1271. doi: 10.1002/nau.23455. Epub 2017 Nov 15.
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Front Physiol. 2017 Feb 6;8:49. doi: 10.3389/fphys.2017.00049. eCollection 2017.
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Am J Physiol Regul Integr Comp Physiol. 2015 Sep 15;309(6):R629-38. doi: 10.1152/ajpregu.00013.2015. Epub 2015 Jul 29.