Andersson Karl-Erik, Boedtkjer Donna B, Forman Axel
Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK 8200 Aarhus N, Denmark.
Department of Biomedicine, Aarhus University, Denmark.
Ther Adv Urol. 2017 Jan;9(1):11-27. doi: 10.1177/1756287216675778. Epub 2016 Nov 4.
The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome. Chronic ischemia-related bladder dysfunction may progress to bladder underactivity and it would be desirable to treat not only lower urinary tract symptoms (LUTS) induced by chronic ischemia, but also the progression of the morphological bladder changes. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension. In turn, this will lead to oxidative stress associated with upregulation of oxidative stress-sensitive genes, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. The phosphodiesterase type 5 (PDE5) inhibitor tadalafil, the α-adrenoceptor (AR) blocker silodosin, the β-AR agonist mirabegron, and the free radical scavenger melatonin, exerted a protecting effect on urodynamic parameters, and on functional and morphological changes of the bladder demonstrable . Since the agents tested are used clinically for relieving LUTS, the results from the animal models seem to have translational value, and may be of relevance for designing clinical studies to demonstrate if the drugs may prevent progression of ischemia-related functional and morphological bladder changes.
人类膀胱的血管供应主要来自膀胱上动脉和膀胱下动脉，后者直接与髂内动脉相连。衰老与血管功能受损相关，血管系统可能在分子、细胞和功能水平上发生变化。盆腔动脉供血不足可能在膀胱功能障碍（如逼尿肌过度活动症（DO）和膀胱过度活动症）的发展中起重要作用。慢性缺血相关的膀胱功能障碍可能进展为膀胱活动减退，不仅需要治疗慢性缺血引起的下尿路症状（LUTS），还需要治疗膀胱形态学变化的进展。对兔和大鼠实验模型的研究表明，盆腔动脉供血不足可能导致膀胱明显缺血，膀胱壁氧张力降低。反过来，这将导致氧化应激，与氧化应激敏感基因上调、毒蕈碱受体活性增加、超微结构损伤和神经退行性变相关。5型磷酸二酯酶（PDE5）抑制剂他达拉非、α-肾上腺素能受体（AR）阻滞剂西洛多辛、β-AR激动剂米拉贝隆和自由基清除剂褪黑素，对尿动力学参数以及膀胱的功能和形态变化均有保护作用。由于所测试的药物在临床上用于缓解LUTS，动物模型的结果似乎具有转化价值，可能与设计临床研究以证明这些药物是否可以预防缺血相关的膀胱功能和形态变化的进展有关。
