慢性脊髓损伤和复发性尿路感染患者膀胱尿路上皮的炎症与屏障功能缺陷

Inflammation and Barrier Function Deficits in the Bladder Urothelium of Patients with Chronic Spinal Cord Injury and Recurrent Urinary Tract Infections.

作者信息

Wu Shu-Yu, Jiang Yuan-Hong, Jhang Jia-Fong, Hsu Yung-Hsiang, Ho Han-Chen, Kuo Hann-Chorng

机构信息

Department of Urology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.

Department of Urology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.

出版信息

Biomedicines. 2022 Jan 20;10(2):220. doi: 10.3390/biomedicines10020220.

Abstract

Patients with spinal cord injury (SCI) commonly experience neurogenic voiding dysfunctions and urinary tract complications, including recurrent urinary tract infections (rUTI). The bladder mucosa barrier function contributes to UTI prevention. This study investigated changes in bladder urothelium protein expression in patients with SCI and rUTI. From June 2011 to November 2017, 23 patients (19 men and 4 women) with chronic SCI were enrolled (mean age: 43 years. Bladder tissues from 6 healthy adults served as the normal control group. Biopsy samples (9 partial cystectomies and 14 bladder biopsies) were analyzed for functional biomarkers using western blot and immunohistochemistry analysis. The barrier function proteins E-cadherin, zonula occludens 1 (ZO-1) and uroplakin III (UPK-3) were significantly reduced, whereas tumor protein p63 (TP63) was significantly increased in SCI patients compared with controls. No significant differences in basal cell progenitor proteins were observed between groups. The proliferation marker Ki-67, the proapoptotic marker BCL-2-associated X protein (BAX), and proinflammatory proteins were increased in patients with SCI compared with controls. No significant differences were observed between SCI patients with and without recently rUTI. These results suggest that SCI patients experience chronic bladder inflammation, increased apoptosis, and reduced barrier function, contributing to rUTI.

摘要

脊髓损伤(SCI)患者常出现神经源性排尿功能障碍和泌尿系统并发症,包括复发性尿路感染(rUTI)。膀胱黏膜屏障功能有助于预防尿路感染。本研究调查了SCI合并rUTI患者膀胱尿路上皮蛋白表达的变化。2011年6月至2017年11月,纳入23例慢性SCI患者(19例男性,4例女性)(平均年龄:43岁)。6名健康成年人的膀胱组织作为正常对照组。使用蛋白质印迹法和免疫组织化学分析法对活检样本(9例部分膀胱切除术和14例膀胱活检)进行功能生物标志物分析。与对照组相比,SCI患者的屏障功能蛋白E-钙黏蛋白、紧密连接蛋白1(ZO-1)和尿血小板蛋白III(UPK-3)显著降低,而肿瘤蛋白p63(TP63)显著升高。两组间基底细胞祖蛋白无显著差异。与对照组相比,SCI患者的增殖标志物Ki-67、促凋亡标志物BCL-2相关X蛋白(BAX)和促炎蛋白增加。近期有rUTI和无rUTI的SCI患者之间未观察到显著差异。这些结果表明,SCI患者存在慢性膀胱炎症、细胞凋亡增加和屏障功能降低,这导致了rUTI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f98/8868780/10c00c716a28/biomedicines-10-00220-g001.jpg

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