Zapała Łukasz, Juszczak Kajetan, Adamczyk Przemysław, Adamowicz Jan, Ślusarczyk Aleksander, Kluz Tomasz, Misiek Marcin, Rogowski Artur, Grzybowska Magdalena Emilia, Stangel-Wójcikiewicz Klaudia, Zaborowski Mikołaj Piotr, Poleszak Ewa, Radziszewski Piotr, Wróbel Andrzej
Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland.
Chair of Urology and Andrology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
Front Mol Biosci. 2022 Jun 21;9:896624. doi: 10.3389/fmolb.2022.896624. eCollection 2022.
The aim of the current study was to determine if phytomedicine (Urox) would reverse retinyl acetate (RA)-induced changes characteristic of bladder overactivity. There were 60 rats divided into the following 4 groups: I-control, II-received RA to induce detrusor overactivity (DO), III-received Urox (840 mg daily for 14 days), and IV-received combination of RA and Urox. The cystometry was performed 2 days after the last dose of Urox. Next, urothelium thickness and biochemical parameter measurements were performed. In group IV, a decrease in basal pressure and detrusor overactivity index was noted when compared to group II. Furthermore, in group IV the following parameters were increased: threshold pressure, voided volume, intercontraction interval, and bladder compliance in comparison with group II. There were significant elevations in c-Fos expression in the neuronal voiding centers in group II, while the expression of c-Fos in group IV was normalized. No significant changes in the values of the analyzed biomarkers in group III were found, while in group II, an elevation in BDNF, NGF, CGRP, ATP, Rho kinase, malondialdehyde, 3-nitrotyrosine, TRPV1, OCT-3, and VAChT and then a decrease in E-cadherin and Z01 were found. A successful restoration of all the abovementioned biomarkers' levels was observed in group IV. Phytomedicine extracts (Urox) were found to be potent in reversing RA-induced changes in several cystometric and biochemical parameters that are determinants of overactive bladder (OAB). The actions of Urox were proved to be dependent on several factors, such as growth factors and several OAB biomarkers but not pro-inflammatory cytokines.
本研究的目的是确定植物药（Urox）是否能逆转醋酸视黄酯（RA）诱导的膀胱过度活动特征性变化。将60只大鼠分为以下4组：I组为对照组，II组接受RA以诱导逼尿肌过度活动（DO），III组接受Urox（每日840 mg，共14天），IV组接受RA和Urox的联合治疗。在最后一剂Urox给药2天后进行膀胱测压。接下来，进行尿路上皮厚度和生化参数测量。与II组相比，IV组的基础压力和逼尿肌过度活动指数降低。此外，与II组相比，IV组的以下参数增加：阈压力、排尿量、收缩间期和膀胱顺应性。II组神经元排尿中枢中c-Fos表达显著升高，而IV组中c-Fos表达恢复正常。III组中分析的生物标志物值无显著变化，而在II组中，发现脑源性神经营养因子（BDNF）、神经生长因子（NGF）、降钙素基因相关肽（CGRP）、三磷酸腺苷（ATP）、 Rho激酶、丙二醛、3-硝基酪氨酸、瞬时受体电位香草酸亚型1（TRPV1）、有机阳离子转运体3（OCT-3）和囊泡乙酰胆碱转运体（VAChT）升高，然后E-钙黏蛋白和紧密连接蛋白1（Z01）降低。在IV组中观察到上述所有生物标志物水平的成功恢复。发现植物药提取物（Urox）在逆转RA诱导的几种膀胱测压和生化参数变化方面具有效力，这些参数是膀胱过度活动症（OAB）的决定因素。事实证明，Urox的作用取决于多种因素，如生长因子和几种OAB生物标志物，但不取决于促炎细胞因子。
