Gonzalez Eric J, Peterson Abbey, Malley Susan, Daniel Mitchel, Lambert Daniel, Kosofsky Michael, Vizzard Margaret A
Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT 05405, USA.
ScientificWorldJournal. 2015;2015:545048. doi: 10.1155/2015/545048. Epub 2015 Apr 20.
We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P ≤ 0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P ≤ 0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P ≤ 0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation.
我们推测环磷酰胺（CYP）诱导的膀胱炎会导致氧化应激，并促使膀胱功能障碍。我们测定了：（1）氧化应激标志物3-硝基酪氨酸（3-NT）、活性氧（ROS）/活性氮（RNS）、炎症调节因子、神经肽降钙素基因相关肽（CGRP）、P物质（Sub P）以及三磷酸腺苷（ATP）的表达，这些物质在尿路炎症过程中发挥作用；（2）使用抗氧化剂Tempol（饮用水中浓度为1 mM）并结合清醒膀胱测压法，研究氧化应激在膀胱功能障碍中的作用。在经CYP处理（4小时或48小时；150 mg/kg，腹腔注射）的大鼠中，膀胱内ROS/RNS和3-NT显著（P≤0.01）增加。CYP处理使膀胱和膀胱测压液中ATP、Sub P和CGRP的表达增加。在经CYP处理的大鼠中，与未使用Tempol的CYP处理大鼠相比，Tempol显著（P≤0.01）增加膀胱容量并降低排尿频率。Tempol显著（P≤0.01）降低经CYP处理大鼠尿路中ATP的表达、3-NT以及ROS/RNS的表达。这些研究表明，减轻CYP诱导的膀胱炎中的氧化应激可改善膀胱功能，并降低氧化应激和炎症标志物。
