Explore the Roles of Urothelial Dysfunction and Chronic Inflammation in the Pathophysiology of Recurrent Bacterial Cystitis

泌尿上皮失調與慢性發炎在反覆細菌性膀胱炎之角色探討

陳毓騏(Yu-Chi Chen) ； 陳忠賢(Chung-Hsien Chen) ； 吳振宇(Chen-Yu Wu) ； 郭漢崇(Hann-Chorng Kuo) ； 林嘉祥(Victor C. Lin)

《輔仁醫學期刊》 13卷2期 (2015/06) Pp. 73-81

https://doi.org/10.3966/181020932015061302002

摘要

背景與目的：此文章之目標是探討泌尿道上皮失調及慢性發炎在反覆細菌性膀胱炎中的角色。方法：我們蒐集30位在一年內發生至少兩次細菌性膀胱炎的女性病患。其中10為女病患有應力性尿失禁的問題但沒有任何膀胱刺激的症狀或泌尿道感染之情型。泌尿道上皮失能的指標如下：TUNEL-細胞凋亡，Ki-67-增值，tryptase staining-肥大細胞活性，E-cadherin以及zonula occludens-1-間隙接頭蛋白表現。這些指標被用來評估泌尿道上皮失能的情形。結果：相較於對照組，實驗組的膀胱黏膜在免疫螢光染色下的E-cadherin 表現降低，但是在肥大細胞以及TUNEL的表現增加。在IHC染色下，E-cadherin, mast cell以及TUNEL在反覆感染的族群與對照組有顯著的統計學上的意義。（p＜0.05）用西方墨點法來分析phospho-p38以及trypatse的表現來證實發炎反應的發生以及Bax蛋白質的表現來證實細胞凋亡的進程。相較於對照組，反覆泌尿道感染的族群的指標表現如下：phospo-p38（約3.6倍），tryptase（約2.0倍）及Bax（約2倍）。結論：相較於對照組，在反覆性膀胱炎的患者，其慢性發炎以及細胞凋亡相關的表現在膀胱黏膜會增加。這些證據顯示在反覆性泌尿道感染的女性患者往往會表現出泌尿道上皮的失能以及慢性發炎。

關鍵字

細菌性膀胱炎 ； 泌尿道上皮失能 ； 免疫螢光染色

並列摘要

Background and purpose: The aim of the study is to explore the roles of urothelial dysfunction and chronic inflammation in the pathophysiology of recurrent bacterial cystitis. Methods: A total of 30 women with recurrent bacteria cystitis at least twice in one year consecutivelywere enrolled in this study. 10 women with stress urinary incontinence without irritative bladder symptoms or any episode of UTI served as the control group. Urothelial dysfunction markers (TUNEL for apoptosis, Ki-67 for proliferation, tryptase staining for mast cell activity, E-cadherin and ZonulaOccludens-1 for junction protein expression) were assessed to explore the possibility of urothelial dysfunction in the bladder mucosa. Results: Compared to those in the controlled group, the bladder mucosa in the experimental group had reduced expression of immuno-fluorescent markers in detecting E-cadherin, but increased expression of mast cell and urothelial dysfunction (TUNEL). The expression of immune-histochemical (IHC) stain with E-cadherin, mast cell and TUNEL of recurrent group had significantdifference when compared to the controlled group, respectively. (p＜ 0.05) Western blot analysis for phospho-p38 and trypatse to confirm the inflammatory events and Bax protein expression to confirm the apoptotic process, which showed that the expressions of phospo-p38 (about 3.6 folds), tryptase (about 2.0 folds) and Bax (about 2 folds) increased in the recurrent UTI specimens compared with the normal control specimens. Conclusion: Increased expression related to chronic inflammation and apoptosis in bladder mucosa of the patients with recurrent urinary tract infection was observed when compared to those in normal control group. This evidence demonstrates that chronic inflammation and urothelial dysfunction are present in most women with recurrent UTI.

並列關鍵字

Bacteria cystitis ； E-cadherin ； Mast cell ； TUNEL ； Phospo-p38 ； Tryptase