Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland.
Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033, Lublin, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Jul;392(7):843-850. doi: 10.1007/s00210-019-01640-3. Epub 2019 Mar 9.
The aims of the study were to determine the effectiveness of blebbistatin (BLEB) on detrusor overactivity (DO) in an animal model induced by retinyl acetate (RA) and, because of potential urothelial permeability, to evaluate the degenerative impact of BLEB on the urothelium. Three days after RA instillation into the urinary bladder, BLEB was administered into the bladder and immediately after cystometric assessment was performed. Furthermore, Evans Blue extravasation into bladder tissue and urothelium thickness were measured. Sixty female Wistar rats were used and randomly assigned to one of four groups (n = 15 in each group): (1) control, (2) RA, (3) BLEB, and (4) RA + BLEB. RA administration induced changes in cystometric parameters reflecting DO, as previously reported. Treatment with BLEB did not significantly alter cystometric parameters in rats which did not receive RA. Administration of BLEB to rats pretreated with RA reversed changes in cystometric parameters induced by RA in basal pressure, threshold pressure, detrusor overactivity index, amplitude of nonvoiding contractions, frequency of nonvoiding contractions, voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. There were no significant differences in Evans Blue extravasation into bladder tissue or urothelium thickness between the groups. The current research provides new data on the possible utility of blebbistatin in the pharmacotherapy of DO, which is an important feature of overactive bladder (OAB). Further studies in human patients with DO/OAB are warranted to confirm these preclinical results.
本研究旨在确定肌球蛋白轻链酶抑制剂（blebbistatin，BLEB）对视黄酸（retinyl acetate，RA）诱导的动物模型中逼尿肌过度活动（detrusor overactivity，DO）的有效性，并且由于潜在的尿路上皮通透性，评估 BLEB 对尿路上皮的退行性影响。RA 注入膀胱 3 天后，将 BLEB 注入膀胱，然后立即进行膀胱测压评估。此外，还测量了膀胱组织和尿路上皮厚度的 Evans Blue 外渗。使用 60 只雌性 Wistar 大鼠，随机分为四组（每组 n=15）：（1）对照组，（2）RA 组，（3）BLEB 组，（4）RA+BLEB 组。如先前报道的，RA 给药引起反映 DO 的膀胱测压参数变化。在未接受 RA 的大鼠中，BLEB 治疗并未显著改变膀胱测压参数。在预先用 RA 处理的大鼠中给予 BLEB 可逆转 RA 引起的膀胱测压参数变化，包括基础压、阈压、逼尿肌过度活动指数、无排尿收缩幅度、无排尿收缩频率、排尿量、容量阈值、收缩间隔、膀胱顺应性和引起无排尿收缩的容量阈值。膀胱组织 Evans Blue 外渗和尿路上皮厚度在各组之间无显著差异。本研究为 BLEB 在 DO 的药物治疗中的可能应用提供了新数据，这是膀胱过度活动症（overactive bladder，OAB）的一个重要特征。需要对患有 DO/OAB 的人类患者进行进一步研究，以确认这些临床前结果。
