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糖尿病伴膀胱过度活动症患者的尿路上皮功能障碍与慢性炎症

Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder.

作者信息

Wang Chung-Cheng, Kuo Hann-Chorng

机构信息

Department of Urology, En Chu Kong Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li, Taiwan.

出版信息

Low Urin Tract Symptoms. 2017 Sep;9(3):151-156. doi: 10.1111/luts.12126. Epub 2016 Mar 28.

Abstract

OBJECTIVES

To investigate urothelial dysfunction, suburothelial inflammation, and muscarinic receptor expression in diabetic patients with overactive bladder (OAB).

METHODS

A total 19 patients with OAB and diabetes mellitus (DM), 14 OAB patients without DM, and 10 healthy control subjects were enrolled in the study. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on the bladder urothelium and suburothelium were performed. Tissue muscarinic receptor M2, M3, and purinergic receptor P2X3 levels were measured by Western blotting. Video urodynamic studies were analyzed in relation to immunofluorescence and western blotting results.

RESULTS

The mean age of the controls, OAB patients without and with DM were comparable (62.9 ± 6.9, 58.4 ± 21.3, and 68.9 ± 11.3 years, respectively, P = 0.25). E-cadherin and mast cell expression in the bladder urothelium samples of the DM-OAB group and the OAB group without DM differed significantly from those of the control group (all P < 0.05). However, immunofluorescence analyses including E-cadherin, mast cells, apoptotic cell counts, and ZO-1 were comparable between OAB patients with and without DM. In addition, M3 muscarinic protein expression in the bladders of OAB patients with and without DM was significantly higher than that in the control subjects. The video urodynamic parameters did not correlate with the immunofluorescence data, M2 and M3 muscarinic receptor data, or P2X3 protein expression.

CONCLUSION

Urothelial dysfunction and chronic suburothelial inflammation may contribute to the pathogeneses of OAB. However, DM does not aggravate the severity of urothelial inflammation in OAB patients.

摘要

目的

研究膀胱过度活动症(OAB)糖尿病患者的尿路上皮功能障碍、黏膜下炎症及毒蕈碱受体表达情况。

方法

本研究纳入了19例患有OAB的糖尿病(DM)患者、14例无DM的OAB患者和10名健康对照者。对膀胱尿路上皮和黏膜下层进行E-钙黏蛋白、紧密连接蛋白-1(ZO-1)、类胰蛋白酶(肥大细胞活化)的免疫荧光染色及凋亡检测。通过蛋白质免疫印迹法测定组织中毒蕈碱受体M2、M3和嘌呤能受体P2X3水平。结合免疫荧光和蛋白质免疫印迹结果对影像尿动力学研究进行分析。

结果

对照组、无DM的OAB患者和有DM的OAB患者的平均年龄相当(分别为62.9±6.9岁、58.4±21.3岁和68.9±11.3岁,P = 0.25)。DM-OAB组和无DM的OAB组膀胱尿路上皮样本中的E-钙黏蛋白和肥大细胞表达与对照组相比有显著差异(均P < 0.05)。然而,有DM和无DM的OAB患者之间包括E-钙黏蛋白、肥大细胞、凋亡细胞计数和ZO-1在内的免疫荧光分析结果相当。此外,有DM和无DM的OAB患者膀胱中M3毒蕈碱蛋白表达均显著高于对照组。影像尿动力学参数与免疫荧光数据、M2和M3毒蕈碱受体数据或P2X3蛋白表达均无相关性。

结论

尿路上皮功能障碍和慢性黏膜下炎症可能参与了OAB的发病机制。然而,DM并不会加重OAB患者尿路上皮炎症的严重程度。

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