Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
J Urol. 2014 May;191(5 Suppl):1597-601. doi: 10.1016/j.juro.2013.09.027. Epub 2014 Mar 26.
We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder.
At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared.
F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change.
Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.
我们推测,由于出口梗阻等临床诊断导致的进行性膀胱功能障碍是由于周期性氧化应激事件引起的。我们假设,测量 F2-异前列腺素,一种脂质过氧化的标志物,可以作为小鼠膀胱氧化应激的生物标志物。
在 5 至 6 周龄时,对去卵巢的雌性小鼠进行 1 种膀胱损伤模型,即部分膀胱出口梗阻或急性膀胱扩张。损伤后的研究时间点包括梗阻后 4、8 和 16 周,以及急性膀胱扩张后 0 至 48 小时。在另一个组中,每隔一天进行短期重复急性膀胱扩张,持续 14 天。使用气相色谱和质谱法分析膀胱样本中的 F2-异前列腺素。比较平均组织 F2-异前列腺素水平。
部分膀胱出口梗阻 4 周后,F2-异前列腺素显著增加,从对照组的 1.46ng/gm 增加到 4 周时的 2.31ng/gm(p=0.01)。部分膀胱出口梗阻 8 和 16 周后,F2-异前列腺素仍显著升高(分别为 2.39 和 2.48ng/gm)。急性膀胱扩张后,与对照组相比,F2-异前列腺素在扩张后立即显著增加(1.6 与 0.75ng/gm,p=0.04)。在接受重复急性膀胱扩张的小鼠中,F2-异前列腺素没有变化。
膀胱组织 F2-异前列腺素的测量反映了氧化应激的进展,主要是在慢性损伤模型中,如部分膀胱出口梗阻。F2-异前列腺素测量在更短期的损伤模型中的有用性需要进一步研究。