Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.
Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.
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DOI：
10.4111/icu.2016.57.4.249
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发表时间：
2016-07
影响因子：
2.3
通讯作者：
Azadzoi KM
中科院分区：
文献类型：
--
作者：
Zhao Z;Azad R;Yang JH;Siroky MB;Azadzoi KM
下尿路症状（LUTS）是男性和女性随着年龄增长而出现的令人烦恼的排尿症状。多种因素和合并症可归因于这个问题，但非梗阻性非神经源性逼尿肌过度活动，逼尿肌活动不足和下尿路症状的潜在机制仍然很大程度上未知。我们的目标是描述慢性膀胱缺血时逼尿肌功能和排尿模式与毒蕈碱受体表达、神经纤维密度和神经超微结构的关系。在雄性Sprague-Dawley大鼠中产生髂动脉粥样硬化和膀胱缺血。在缺血后8周和16周，记录清醒大鼠的排尿模式和膀胱测压图，然后在全身麻醉下测量膀胱血流量和非排尿性自发收缩。对膀胱组织进行Western印迹、免疫染色和透射电子显微镜检查。膀胱对缺血性损伤的反应取决于缺血的持续时间。排尿模式和膀胱测压的变化，在8周的缺血表明逼尿肌过度活动，而排尿行为和膀胱测压在16周的缺血暗示异常逼尿肌功能类似于活动不足。在缺血8周和16周后发现毒蕈碱M2受体上调。在缺血16周时检测到M3下调和M1上调。缺血8周和16周后，分别发现神经结构损伤和明显的神经变性。长期缺血可能是膀胱过度活动症进展为类似逼尿肌活动不足的功能障碍模式的介导变量。其机制似乎涉及M1、M2和M3受体的差异表达、神经结构损伤和神经纤维的进行性丢失。
Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia. Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy. Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively. Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers.