Lu Yutao, Manson Scott R, de Araujo Isabela Bastos Binotti Abreu, Austin Paul F, Djurhuus Jens C, Olsen L Henning, Nørregaard Rikke
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Urology, Baylor College of Medicine, Houston, TX, United States.
Front Med (Lausanne). 2022 May 12;9:892746. doi: 10.3389/fmed.2022.892746. eCollection 2022.
Bladder outlet obstruction (BOO) induces bladder dysfunction and altered bladder architecture. Irrespective of the release of the obstruction, persistent bladder dysfunction severely affects the quality of life. A better understanding of the repair process offers an opportunity to enhance postintervention management. We subsequently evaluated the postobstructive repair process in mice subjected to 24 h BOO followed by release. Male and female mice bladders were obstructed for 24 h by placing a clip around the bladder neck. After the release of obstruction, the mice were studied for 3, 7, and 14 days to observe the bladder repair process over time. Voiding frequency and volume were recorded using the voiding spot assay, and the transcutaneous glomerular filtration rate (tGFR) was measured. Fibrogenesis and associated gene expressions and altered protein levels were evaluated in the bladder using histology, quantatative polymerase chain reaction (qPCR), and Western blot analyses. Bladder wall thickness was increased in both genders over time but occurred later in female mice. Moreover, collagen deposition in the smooth muscle layer increased over time in both genders. Male mice showed a decreased average voided volume at 3 days post release, while female mice showed no significant change during the time course. Fibrosis-related molecular events, including upregulation of fibronectin (FN) protein and Collagen-3 (Col-3) mRNA expression, were transient and normalized again at 14 days in both genders. Transforming growth factor-β (TGF-β) and bone morphogenic protein (BMP)-7 mRNA expressions were upregulated at 14 days post release in both genders. Transcutaneous GFR remained normal during the time course. Release of 24 h BOO initiated a bladder remodeling process. The animal model enables a wide range of experiments to study bladder remodeling, and gender differences offer potential targets for understanding bladder fibrosis and adaptation with BOO.
膀胱出口梗阻（BOO）会导致膀胱功能障碍和膀胱结构改变。无论梗阻是否解除，持续性膀胱功能障碍都会严重影响生活质量。更好地了解修复过程为改善干预后的管理提供了机会。我们随后评估了在经历24小时BOO后再解除梗阻的小鼠的梗阻后修复过程。通过在膀胱颈部放置夹子，对雄性和雌性小鼠的膀胱进行24小时梗阻。梗阻解除后，对小鼠进行3天、7天和14天的研究，以观察随时间推移的膀胱修复过程。使用排尿点测定法记录排尿频率和尿量，并测量经皮肾小球滤过率（tGFR）。使用组织学、定量聚合酶链反应（qPCR）和蛋白质印迹分析评估膀胱中的纤维化形成、相关基因表达和蛋白质水平变化。随着时间的推移，两性的膀胱壁厚度均增加，但雌性小鼠出现得较晚。此外，两性平滑肌层中的胶原蛋白沉积均随时间增加。雄性小鼠在解除梗阻后3天平均排尿量减少，而雌性小鼠在整个时间过程中无显著变化。纤维化相关分子事件，包括纤连蛋白（FN）蛋白上调和胶原蛋白-3（Col-3）mRNA表达，在两性中均为短暂性，14天时再次恢复正常。两性在解除梗阻后14天，转化生长因子-β（TGF-β）和骨形态发生蛋白（BMP）-7 mRNA表达均上调。在整个时间过程中，经皮GFR保持正常。24小时BOO的解除启动了膀胱重塑过程。该动物模型能够进行广泛的实验来研究膀胱重塑，性别差异为理解膀胱纤维化和BOO适应提供了潜在靶点。
