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委陵菜水提物减轻环磷酰胺诱导的大鼠出血性膀胱炎。

Potentilla chinensis aqueous extract attenuates cyclophosphamide-induced hemorrhagic cystitis in rat model.

机构信息

Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, M. Curie Skłodowskiej 9, 85-094, Bydgoszcz, Poland.

Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

出版信息

Sci Rep. 2022 Jul 29;12(1):13076. doi: 10.1038/s41598-022-17393-8.

Abstract

Cyclophosphamide (CYP) damages all mucosal defence lines and induces hemorrhagic cystitis (HC) leading to detrusor overactivity. Patients who undergo combined chemio-radiotherapy are at higher risk of HC. Potentilla chinensis extract (PCE) prevent oxidative stress-dependent diseases. Thus, the aim of the study was to investigate the effect of PCE on urinary bladder function in CYP-induced HC in preclinical study. 60 rats were divided into 4 groups, as follows: I-control, II-rats with CYP-induced HC, III-rats received PCE in dose of 500 mg/kg, and IV-rats with CYP-induced HC which received PCE in dose of 500 mg/kg. PCE or vehicle were administered orally for 14 days. The cystometry was performed 3 days after the last dose of the PCE. Next, urothelium thickness and oedema measurement and biochemical analyses were performed. Cyclophosphamide induced hemorrhagic cystitis. PCE had no influence on the urinary bladder function and micturition cycles in normal rats. PCE diminished the severity of CYP-induced hemorrhagic cystitis. In the urothelium the cyclophosphamide induced the elevation of CGRP, TNF-α, IL-6, IL-1β, OTC NIT, and MAL. Also, the level of T-H protein, HB-EGF, and ZO1 was decreased. Moreover, the level of ROCK1 and VAChT in detrusor muscle increased. cyclophosphamide caused an increased concentration of BDNF and NGF in the urine. In turn, PCE in cyclophosphamide-induced hemorrhagic cystitis caused a reversal of the described biochemical changes within urothelium, detrusor muscle and urine. PCE attenuates detrusor overactivity. In conclusion, our results revealed that PCE attenuates detrusor overactivity in case of cyclophosphamide-induced hemorrhagic cystitis. The potential properties of PCE appear to be important in terms of preventing of oxidative stress-dependent dysfunction of urinary bladder. PCE may become a potential supportive treatment in patient to whom cyclophosphamide-based chemotherapy is used.

摘要

环磷酰胺(CYP)损伤所有黏膜防御线,并诱导出血性膀胱炎(HC),导致逼尿肌过度活动。接受化疗和放疗联合治疗的患者发生 HC 的风险更高。中药提取物(PCE)可预防氧化应激相关疾病。因此,本研究旨在探讨 PCE 对 CYP 诱导的 HC 中膀胱功能的影响。将 60 只大鼠分为 4 组,如下:I-对照组,II-CYP 诱导的 HC 大鼠,III-PCE 剂量为 500mg/kg 的大鼠,IV-CYP 诱导的 HC 大鼠,PCE 剂量为 500mg/kg。PCE 或载体口服给药 14 天。最后一次 PCE 给药后 3 天进行膀胱测压。然后进行尿路上皮厚度和水肿测量以及生化分析。环磷酰胺诱导出血性膀胱炎。PCE 对正常大鼠的膀胱功能和排尿周期没有影响。PCE 减轻了 CYP 诱导的出血性膀胱炎的严重程度。在尿路上皮中,环磷酰胺引起 CGRP、TNF-α、IL-6、IL-1β、OTC NIT 和 MAL 水平升高。此外,T-H 蛋白、HB-EGF 和 ZO1 的水平降低。此外,逼尿肌中 ROCK1 和 VAChT 的水平增加。环磷酰胺导致尿液中 BDNF 和 NGF 的浓度增加。相反,PCE 在 CYP 诱导的 HC 中引起尿路上皮、逼尿肌和尿液中描述的生化变化的逆转。PCE 可减轻逼尿肌过度活动。总之,我们的结果表明,PCE 可减轻环磷酰胺诱导的出血性膀胱炎引起的逼尿肌过度活动。PCE 的潜在特性在预防与氧化应激相关的膀胱功能障碍方面似乎很重要。PCE 可能成为接受环磷酰胺为基础的化疗的患者的潜在辅助治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ef5/9338276/9de99d073d75/41598_2022_17393_Fig1_HTML.jpg

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