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白三烯 D4 受体拮抗剂孟鲁司特减轻硫酸鱼精蛋白诱导的大鼠膀胱变化。

Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate-induced changes in rat urinary bladder.

机构信息

Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkey.

出版信息

BJU Int. 2011 Apr;107(8):1320-5. doi: 10.1111/j.1464-410X.2010.09532.x.

DOI:10.1111/j.1464-410X.2010.09532.x
PMID:20735385
Abstract

UNLABELLED

What's known on the subject? and What does the study add? The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry.

OBJECTIVE

• To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl-containing leukotrienes, on protamine sulphate (PS)-induced changes in rat urinary bladder.

MATERIALS AND METHODS

• Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h. • In the PS-applied and ML-treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days. • The urinary bladder was investigated for general morphology under a light microscope. • Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry.

RESULTS

• Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope. • Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions. • In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions. • The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings.

CONCLUSION

• Montelukast appears to have a protective function in the bladder injury model via the anti-inflammatory effects of this leukotriene receptor antagonist.

摘要

目的

• 研究孟鲁司特(ML),一种白三烯受体拮抗剂,已被证明能有效抑制含半胱氨酸的白三烯的作用,对硫酸鱼精蛋白(PS)诱导的大鼠膀胱变化的影响。

材料和方法

• Wistar 雌性大鼠通过导管插入术并经膀胱内灌注 PBS(对照组)或 PBS 中溶解的 PS(PS 组),24 小时内两次。• 在 PS 应用和 ML 治疗组(PS + ML 组)中,在 10mg/kg PS 注入后,每天两次腹腔注射 ML 共 3 天。• 用光学显微镜研究膀胱的一般形态。• 用免疫组织化学法观察肥大细胞的分布和激活。也用免疫组织化学法鉴定尿路上皮蛋白的分布。

结果

• 用透射电子显微镜用钌红(RR)染色技术观察到糖胺聚糖(GAG)和尿路上皮通透性的改变,用扫描电子显微镜观察到腔上皮结构的表面变化。• 分析丙二醛(MDA)和谷胱甘肽(GSH)的浓度。在 PS 组中,可见退化的尿路上皮,尿路上皮蛋白分布不规则,炎症细胞浸润增加,颗粒状和活化的肥大细胞数量增加,GAG 不规则,RR 渗透到细胞间隙,紧密连接扩张。• 在 PS + ML 组中,尿路上皮蛋白分布相对规则,炎症细胞浸润减少,粘膜中活化和颗粒状肥大细胞数量减少,GAG 规则,RR 无渗透到细胞间隙,大多数区域的紧密连接规则。• PS + ML 组 MDA 显著减少,GSH 浓度增加,与组织学发现一致。

结论

• 孟鲁司特通过这种白三烯受体拮抗剂的抗炎作用,似乎对膀胱损伤模型具有保护作用。

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