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环磷酰胺诱导的大鼠出血性膀胱炎模型中的高压氧治疗

Hyperbaric oxygen therapy in a rat model of cyclophosphamide-induced hemorrhagic cystitis.

作者信息

Makar Cagri Can, Sanli Elif, Koral Gizem, Hurdogan Ozge, Gumus Ahmet Veysel, Gunver Mehmet Guven, Ozluk Yasemin, Aktas Samil

机构信息

Istanbul Faculty of Medicine, Department of Underwater and Hyperbaric Medicine, Istanbul University, Turgut Özal Avenue No: 118, 34093, Fatih, Istanbul, Turkey.

Aziz Sancar Institute of Experimental Medicine, Department of Neuroscience, Istanbul University, Fatih, Istanbul, Turkey.

出版信息

Int Urol Nephrol. 2025 Jul 17. doi: 10.1007/s11255-025-04650-8.

Abstract

OBJECTIVE

To evaluate the effects of hyperbaric oxygen therapy (HBOT) on inflammation, oxidative stress, and bladder damage in a cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) rat model.

METHODS

Forty male Wistar albino rats received a single intraperitoneal dose of 200 mg/kg CP to induce HC. Rats were assigned to either the HBOT or control groups and sacrificed on days 3, 7, and 14. The HBOT group received 6, 14, or 28 sessions of 100% oxygen at 2.4 ATA for 90 min. Outcomes included mortality, weight loss, bladder weight, macroscopic edema and hemorrhage scores, histopathology, Ki-67 immunostaining, and levels of cytokines (IL-1β, IL-4, IL-6, MCP-1, TNF-α) and malondialdehyde in bladder tissue, serum, and urine. Cytokines were quantified using the Luminex assay and malondialdehyde by ELISA.

RESULTS

Mortality and weight loss were similar between groups. On day 3, the HBOT group showed significantly lower bladder weights and hemorrhage scores (p < 0.01), with no significant differences in edema. On day 7, IL-1β and MCP-1 levels were higher in the HBOT group (p = 0.02). Malondialdehyde levels were significantly elevated in the control group on day 3. Histopathological and other cytokine findings showed no significant differences.

CONCLUSIONS

HBOT may provide early but transient benefits in alleviating HC based on macroscopic findings; however, these effects were not supported by sustained histopathological or molecular improvements. The high-dose CP model may have masked the potential therapeutic effects of HBOT. Further studies using lower or fractionated CP dosing and extended observation periods are warranted to better evaluate the therapeutic potential of HBOT.

摘要

目的

评估高压氧疗法(HBOT)对环磷酰胺(CP)诱导的出血性膀胱炎(HC)大鼠模型炎症、氧化应激及膀胱损伤的影响。

方法

40只雄性Wistar白化大鼠腹腔注射单次剂量200mg/kg的CP以诱导HC。将大鼠分为HBOT组或对照组,并在第3、7和14天处死。HBOT组接受2.4ATA的100%氧气治疗90分钟,共6、14或28次。观察指标包括死亡率、体重减轻、膀胱重量、肉眼可见的水肿和出血评分、组织病理学、Ki-67免疫染色,以及膀胱组织、血清和尿液中细胞因子(IL-1β、IL-4、IL-6、MCP-1、TNF-α)和丙二醛的水平。细胞因子采用Luminex检测法进行定量,丙二醛采用ELISA法检测。

结果

两组之间的死亡率和体重减轻情况相似。在第3天,HBOT组的膀胱重量和出血评分显著较低(p<0.01),水肿无显著差异。在第7天,HBOT组的IL-1β和MCP-1水平较高(p=0.02)。在第3天,对照组的丙二醛水平显著升高。组织病理学和其他细胞因子结果无显著差异。

结论

基于肉眼观察结果,HBOT在缓解HC方面可能具有早期但短暂的益处;然而,这些效果并未得到持续的组织病理学或分子水平改善的支持。高剂量CP模型可能掩盖了HBOT的潜在治疗效果。有必要进一步开展使用较低剂量或分次给药的CP以及延长观察期的研究,以更好地评估HBOT的治疗潜力。

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