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在硫酸鱼精蛋白和细菌内毒素诱导的慢性膀胱炎大鼠膀胱模型中肥大细胞的活化及对托特罗定的反应。

Mast cell activation and response to tolterodine in the rat urinary bladder in a chronic model of intravesical protamine sulfate and bacterial endotoxin-induced cystitis.

作者信息

Choi Bo-Hwa, Jin Long-Hu, Kim Khae-Hawn, Han Jee-Young, Kang Ju-Hee, Yoon Sang-Min, Park Chang-Shin, Lee Tack

机构信息

Department of Pharmacology, Inha University College of Medicine by BK 21 Project, Incheon 400-711, South Korea.

Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

出版信息

Mol Med Rep. 2014 Aug;10(2):670-6. doi: 10.3892/mmr.2014.2262. Epub 2014 May 22.

Abstract

The aim of the present study was to use an animal model of interstitial cystitis (IC) in order to investigate the histology and function of the bladder, with a particular focus on mast cell degranulation and response to detrusor overactivity (DO) to tolterodine. A total of 18 female Sprague‑Dawley rats were used. In 12 rats, lipopolysaccharide (LPS) was intravesically instilled following the induction of IC by protamine sulfate (PS) and six rats were subjected to sham instillations. Following 1 month, cystometry was performed. The effects of tolterodine were tested in half of the animals with IC. All rats in the IC group demonstrated DO during the filling phase and no significant changes in the frequency or pressure compared with that following tolterodine injection were identified. Histological examination revealed a significant increase in the total number of infiltrated mast cells in IC rats compared with that in the sham rats (P<0.05). Degranulated mast cells were evident in 80% of rats with IC; however, they were not apparent in the sham rats. Urinary bladder inflammation, similar to that in human IC in terms of degranulated mast cells and bladder function, was induced in rats. The animal model used in the present study provided insight into the pathophysiological mechanisms underlying the ineffectiveness of anticholinergics in patients with overlapping IC and overactive bladder (OAB).

摘要

本研究的目的是使用间质性膀胱炎(IC)动物模型来研究膀胱的组织学和功能,特别关注肥大细胞脱颗粒以及膀胱逼尿肌过度活动(DO)对托特罗定的反应。总共使用了18只雌性Sprague-Dawley大鼠。其中12只大鼠在经硫酸鱼精蛋白(PS)诱导IC后膀胱内注入脂多糖(LPS),另外6只大鼠进行假注入。1个月后,进行膀胱测压。在一半的IC动物中测试托特罗定的效果。IC组所有大鼠在充盈期均表现出DO,与注射托特罗定后相比,频率或压力无显著变化。组织学检查显示,与假手术大鼠相比,IC大鼠中浸润的肥大细胞总数显著增加(P<0.05)。80%的IC大鼠中有明显的脱颗粒肥大细胞;然而,在假手术大鼠中未观察到。在大鼠中诱导出了与人类IC在脱颗粒肥大细胞和膀胱功能方面相似的膀胱炎症。本研究中使用的动物模型为深入了解抗胆碱能药物对合并IC和膀胱过度活动症(OAB)患者无效的病理生理机制提供了线索。

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