Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China.
Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, 710061 Xi'an, Shaanxi, China.
Arch Esp Urol. 2023 Feb;76(1):56-64. doi: 10.56434/j.arch.esp.urol.20237601.5.
The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue.
Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways.
CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways.
Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis.
出血性膀胱炎（HC）的主要病理变化为膀胱炎症、膀胱上皮损伤和肥大细胞浸润。曲昔派特已被证实对 HC 具有保护作用，但具体病因仍不清楚。本研究旨在评估曲昔派特在出血性膀胱炎组织中的作用机制。
利用环磷酰胺（CTX）构建 HC 大鼠模型，并用不同剂量的曲昔派特处理大鼠。采用 Western blot 检测曲昔派特对膀胱炎大鼠炎症因子和氧化应激因子表达的影响，以及 Toll 样受体 4/核转录因子-κB（TLR-4/NF-κB）和 Janus 激酶 1/信号转导和转录激活因子 3（JAK1/STAT3）通路相关蛋白的表达。
CTX 诱导的大鼠膀胱炎伴有明显的组织损伤和膀胱湿重比增加，肥大细胞数量和胶原纤维增生增加，与对照组相比。曲昔派特呈浓度依赖性改善 CTX 诱导的损伤。此外，CTX 诱导氧化应激和炎症损伤，而曲昔派特可减轻这些损伤。此外，曲昔派特通过抑制 TLR-4/NF-κB 和 JAK1/STAT3 信号通路改善 CTX 诱导的膀胱炎。
综上所述，曲昔派特通过调节 TLR-4/NF-κB 和 JAK1/STAT3 信号通路改善环磷酰胺诱导的出血性膀胱炎。这些发现对研究出血性膀胱炎药物治疗的分子机制具有重要意义。
