Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Urology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan.
Neurourol Urodyn. 2020 Jan;39(1):108-115. doi: 10.1002/nau.24170. Epub 2019 Oct 3.
To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI).
Cystometry and external urethral sphincter-electromyography were performed under an awake condition in 4-week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen-activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6-S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 μL/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor-treated SCI mice as well as from CSF-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) transcripts by real-time polymerase chain reaction.
In p38 MAPK inhibitor-treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post-void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF-treated SCI mice. The expression of TRPV1, TNF-α, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment.
The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.
研究 p38 丝裂原活化蛋白激酶（MAPK）在脊髓损伤（SCI）小鼠下尿路功能障碍中的作用。
在清醒状态下对 4 周龄 SCI 雌性小鼠进行膀胱测压和尿道外括约肌肌电图检查。SCI 后 2 周，将连接有充满 p38 MAPK 抑制剂或人工脑脊液（CSF）的渗透泵的导管植入 L6-S1 脊髓蛛网膜下腔，以 0.51μL/h 的输注速度持续鞘内灌注 2 周，然后进行尿动力学研究。然后从 CSF 和 p38 MAPK 抑制剂处理的 SCI 小鼠以及 CSF 处理的正常（脊髓完整）小鼠的 CSF 中取出 L6 背根神经节，通过实时聚合酶链反应评估瞬时受体电位阳离子通道亚家族 V 成员 1（TRPV1）、肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）转录本的水平。
与 CSF 处理的 SCI 小鼠相比，p38 MAPK 抑制剂处理的 SCI 小鼠在膀胱充盈过程中出现非排空收缩、膀胱容量和残余尿量明显减少，而排尿压力和排空效率明显增加。与脊髓完整小鼠相比，SCI 小鼠中 TRPV1、TNF-α 和 iNOS 信使 RNA 的表达增加，而 p38 MAPK 抑制剂处理后表达明显降低。
膀胱感觉神经元或脊髓中的 p38 MAPK 信号通路在 SCI 后逼尿肌过度活动和排尿效率低下等储尿和排尿问题中起重要作用。
