Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder
Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder
复制标题
早期的排尿功能障碍通过改变膀胱中的毒蕈碱能和嘌呤能信号传导导致下尿路功能障碍。
DOI：
10.1152/ajprenal.00154.2018
复制
发表时间：
2018-11-01
影响因子：
4.2
通讯作者：
Wilcox, Duncan T.
中科院分区：
文献类型：
--
作者：
Iguchi, Nao;Malykhina, Anna P.;Wilcox, Duncan T.
下尿路功能障碍 (LUTD) 是儿童的常见问题，占儿科泌尿外科门诊就诊人数的 40%。改进的诊断和干预措施为许多患者带来了更好的结果，而一些儿童则没有得到治疗或对治疗没有成功的反应。此外，这些患者中的许多人在青少年时期就被儿科泌尿科医生迷失了。而晚年生活的结果很大程度上仍不得而知。研究表明儿童期 LUTD 与随后的成人尿路症状有关。然而。早期的 LUTD 是否以及如何归因于这些患者晚年的泌尿系统症状仍有待阐明。在当前的研究中，我们使用新生儿母体分离 (NMS) 方案研究了小鼠早期排尿扰动对膀胱功能的影响。与对照组小鼠相比，NMS 组小鼠在晚年表现出自主排尿行为发展迟缓、功能性膀胱容量显着减少以及膀胱过度活动。逼尿肌平滑肌的体外评估和分子研究表明，与对照组相比，NMS 小鼠逼尿肌收缩力的毒蕈碱贡献减少，而嘌呤能贡献增加。这些结果表明，生命早期的膀胱功能障碍干扰了自主排尿控制的正常成熟，并促进了后期的 LUTD，这至少部分归因于膀胱中毒蕈碱和嘌呤能信号的改变。
Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40% of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, whereas some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years. and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However. whether and how early life LUTD attributes to urinary symptoms in those patients later in life remains to be elucidated. In the current study, we investigated the effects of early life voiding perturbation on bladder function using a neonatal maternal separation (NMS) protocol in mice. The NMS group displayed a delayed development of voluntary voiding behavior, a significant reduction of functional bladder capacity, and bladder overactivity compared with control mice later in life. In vitro evaluation of detrusor smooth muscle and molecular study showed a decrease in muscarinic contribution alongside an increase in purinergic contribution in detrusor contractility in NMS mice compared with control group. These results suggest that early life bladder dysfunction interfered with the normal maturation of the voluntary micturition control and facilitated LUTD in a later stage, which is at least partly attributed to an alteration of muscarinic and purinergic signaling in the urinary bladder.