Celik-Ozenci Ciler, Ustunel Ismail, Erdogru Tibet, Seval Yasemin, Korgun Emin Turkay, Baykara Mehmet, Demir Ramazan
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Campus, 07070, Antalya, Turkey.
Acta Histochem. 2006;107(6):443-51. doi: 10.1016/j.acthis.2005.09.004. Epub 2005 Oct 25.
The present study was undertaken to evaluate alterations in uroepithelial cell junctional complexes in partial bladder outlet obstruction (PBOO) of rat bladders using ultrastructural morphometry and immunohistochemistry, and to determine whether selective COX-2 inhibitors have any effects on these structures. A total of 18 male rats were separated into three groups of six rats each: (1) sham-operated animals served as controls; (2) a PBOO group, without further treatment (3) and a group that immediately after PBOO, received treatment for 4 weeks with oral Celecoxib, a selective COX-2 inhibitor. Uroepithelial cell junctions were evaluated using transmission electron microscopy combined with morphometry. Results were also assessed by E-cadherin and alpha-catenin immunohistochemistry. Morphometrical analysis of ultrastructural evaluations revealed that 4 weeks of PBOO caused a significant reduction in the electron density of zonula adherens and zonula occludens junctional complexes. Moreover, some desmosomes located between the deeper cells of the uroepithelium showed signs of disintegration. Selective COX-2 inhibitor treatment during 4 weeks of PBOO showed protective effects on adherens and occludens junctions, as well as on desmosomes. Immunohistochemical analysis of E-cadherin confirmed that the decreased E-cadherin immunolabelling in 4 weeks of PBOO was prevented by selective COX-2 inhibitor treatment. Based on ultrastructural morphometrical analysis, we conclude that PBOO alone and in combination with selective COX-2 inhibitors can have considerable effects on uroepithelial cellular junctions. Our findings provide a novel area of investigation regarding the selective use of COX-2 inhibitors following PBOO.
本研究旨在利用超微结构形态计量学和免疫组织化学评估大鼠膀胱部分膀胱出口梗阻(PBOO)时尿路上皮细胞连接复合体的变化,并确定选择性COX-2抑制剂是否对这些结构有任何影响。总共18只雄性大鼠被分成三组,每组6只:(1)假手术动物作为对照组;(2)PBOO组,不进行进一步治疗;(3)一组在PBOO后立即接受选择性COX-2抑制剂塞来昔布口服治疗4周。使用透射电子显微镜结合形态计量学评估尿路上皮细胞连接。结果也通过E-钙黏蛋白和α-连环蛋白免疫组织化学进行评估。超微结构评估的形态计量学分析显示,4周的PBOO导致黏着小带和紧密连接复合体的电子密度显著降低。此外,位于尿路上皮较深层细胞之间的一些桥粒显示出解体的迹象。在PBOO的4周期间进行选择性COX-2抑制剂治疗对黏着连接和紧密连接以及桥粒均显示出保护作用。E-钙黏蛋白的免疫组织化学分析证实,选择性COX-2抑制剂治疗可防止PBOO 4周时E-钙黏蛋白免疫标记降低。基于超微结构形态计量学分析,我们得出结论,单独的PBOO以及与选择性COX-2抑制剂联合使用均可对尿路上皮细胞连接产生相当大的影响。我们的研究结果为PBOO后选择性使用COX-2抑制剂提供了一个新的研究领域。