Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005 Warsaw, Poland.
Int J Mol Sci. 2021 May 29;22(11):5853. doi: 10.3390/ijms22115853.
The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T-H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.
本研究旨在确定熊果酸是否能有效作用于环磷酰胺（CYP）诱导的大鼠膀胱炎模型。在给予 CYP（单次剂量 200mg/kg，腹腔内注射）、熊果酸（30mg/kg/天，连续 14 天，口服灌胃）或 CYP 加熊果酸后进行实验，在此期间进行清醒膀胱测压、尿路上皮厚度和膀胱水肿测量以及选择生物标志物分析。与 CYP 组相比，同时接受 CYP 和熊果酸治疗的大鼠膀胱基础压、逼尿肌过度活动指数、无逼尿肌收缩振幅、无逼尿肌收缩频率和压力曲线下面积均下降。此外，该组还发现阈值压力、排空量、收缩间间隔、膀胱顺应性和诱发 NVC 的体积阈值显著增加。熊果酸的给药成功恢复了膀胱尿路上皮（BDNF、CGRP、OCT-3、IL-1β、IL-6、NGF、硝基酪氨酸、丙二醛、TNF-α、SV2A、SNAP23、SNAP25、PAC-1、ORM1、occludin、IGFBP-3、HB-EGF、T-H 蛋白、Z01 和 HPX）和逼尿肌肌肉（Rho 激酶和 VAChT）中生物标志物在 CYP 处理大鼠中的浓度。最后，熊果酸显著降低了尿路上皮厚度和膀胱水肿。熊果酸被证明是 CYP 诱导的膀胱炎大鼠模型中的一种有效药物。
