Park Jee Soo, Jung Hae Do, Cho Young Sam, Jin Mei Hua, Hong Chang Hee
Department of Urology, Yonsei University College of Medicine, Seoul, Korea.
Department of Urology, Yongin Severance Hospital, Yonsei University Health System, Yongin, Korea.
Int Neurourol J. 2018 Sep;22(3):169-176. doi: 10.5213/inj.1836020.101. Epub 2018 Sep 28.
To evaluate whether mild chemical irritation of the bladder in neonatal rats is associated with persistent vanilloid receptor transient receptor potential vanilloid subfamily 1 (TRPV1) activity in adult rats.
Female Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder sensitization via intravesical infusion of 0.2% acetic acid in saline with or without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of rats (control [group 1], bladder sensitization [group 2], and bladder desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were also evaluated.
The bladder sensitization group showed more frequent voiding contractions. TRPV1 expression in adult bladder tissue was elevated in group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1 immunoreactivity.
We found a significant association between neonatal bladder sensitization and persistent TRPV1 activity in adult rats. This is the first study to focus on the underlying pathogenesis of bladder overactivity from childhood to adulthood. Our findings could lead to the development of new strategies for the treatment and prevention of adult urinary symptoms arising from childhood urinary tract dysfunction.
评估新生大鼠膀胱的轻度化学刺激是否与成年大鼠中香草酸受体瞬时受体电位香草酸亚家族1(TRPV1)的持续活性相关。
使用雌性Sprague-Dawley大鼠。10日龄的幼鼠通过膀胱内输注0.2%乙酸盐水溶液进行膀胱致敏,其中部分大鼠在致敏前先用辣椒素进行膀胱脱敏。8周后,3组大鼠(对照组[第1组]、膀胱致敏组[第2组]和膀胱脱敏组[第3组])接受膀胱测压。还评估了膀胱组织炎症以及膀胱组织和背根神经节(DRG)中TRPV1的表达。
膀胱致敏组排尿收缩更频繁。第2组成年膀胱组织中TRPV1表达升高。第2组膀胱和DRG中的TRPV1 mRNA水平显著高于第1组。此外,第2组中显示TRPV1免疫反应性的DRG神经元(通过逆行标记物快蓝摄取鉴定)明显更多。
我们发现新生大鼠膀胱致敏与成年大鼠中TRPV1的持续活性之间存在显著关联。这是第一项关注从儿童期到成年期膀胱过度活动潜在发病机制的研究。我们的发现可能会导致开发新的策略来治疗和预防因儿童期尿路功能障碍引起的成人泌尿系统症状。