Division of Urology, Department of Surgery, McGill University, Montreal, Quebec, Canada.
Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
Neurourol Urodyn. 2018 Jun;37(5):1549-1558. doi: 10.1002/nau.23488. Epub 2018 Apr 18.
Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function.
Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks. Conscious cystometry was performed at the end of this period. Bladders were collected and used for contractility studies and morphological assessment. Two-way ANOVA was performed to compare between the two strains and student t-tests to compare treatment groups within each strain.
Compared to SD rats, Dahl rats showed signs of bladder dysfunction. Succinate treatment led to higher urinary succinate levels and lower bladder capacities compared to saline-treated animals. In SD rats, this was associated with higher collagen content, lower GPR91 expression and an altered bladder nerve profile in the bladder. In succinate-treated Dahl rats, detrusor contractility was reduced and associated with decreased cholinergic innervation and increased collagen content.
It is suggested that succinate negatively affects bladder function via effects through its receptor, GPR91, and that its effects are enhanced in the presence of metabolic disturbance. These findings contribute to our understanding of the pathophysiology of bladder dysfunction, specifically in a metabolic syndrome setting.
琥珀酸及其受体 GPR91 与代谢综合征的多个方面有关。由于 GPR91 在膀胱中表达，本研究旨在展示慢性琥珀酸水平升高对膀胱功能的影响。
健康的 Sprague-Dawley（SD）大鼠和高血压 Dahl 大鼠每天接受腹腔注射生理盐水或琥珀酸（50mg/kg），持续 4 周。在此期间结束时进行清醒膀胱测压。收集膀胱用于收缩性研究和形态评估。采用双因素方差分析比较两种品系之间的差异，采用学生 t 检验比较每种品系中治疗组之间的差异。
与 SD 大鼠相比，Dahl 大鼠表现出膀胱功能障碍的迹象。与生理盐水处理的动物相比，琥珀酸处理导致尿液琥珀酸水平升高和膀胱容量降低。在 SD 大鼠中，这与胶原含量增加、GPR91 表达降低以及膀胱神经形态改变有关。在琥珀酸处理的 Dahl 大鼠中，逼尿肌收缩力降低，与胆碱能神经支配减少和胶原含量增加有关。
琥珀酸通过其受体 GPR91 对膀胱功能产生负面影响，并且在存在代谢紊乱的情况下其作用会增强。这些发现有助于我们了解膀胱功能障碍的病理生理学，特别是在代谢综合征环境中。
