Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A clinical and experimental study
Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A clinical and experimental study
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DOI：
10.1002/nau.22542
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发表时间：
2015-06-01
影响因子：
2
通讯作者：
Cruz, Francisco
中科院分区：
文献类型：
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作者：
Charrua, Ana;Pinto, Rui;Cruz, Francisco
目的评价膀胱痛综合征/间质性膀胱炎(BPS/IC)患者的交感神经活动，并探讨慢性肾上腺素能刺激是否导致BPS/IC样膀胱改变。方法对BPS/IC患者和年龄、体重指数相匹配的健康志愿者进行倾斜试验，测定血浆和24小时尿儿茶酚胺。雌性Wistar大鼠皮下注射去氧肾上腺素(14天)。分析疼痛行为、脊髓Fos表达、尿斑、排出粪便小球的数量、反射性膀胱收缩频率和尿路上皮高度。台盼蓝染色检测尿路上皮通透性。研究了尿路上皮细胞对caspase3和Bax的免疫反应性以及尿路上皮下神经对α1肾上腺素受体和TRPV1的免疫反应性。测定尿路下皮内肥大细胞的数量。在内毒素诱导的大鼠膀胱炎模型上，分析尿儿茶酚胺和囊泡单胺转运体2(VMAT2)在膀胱神经中的表达。结果倾斜试验显示交感神经活动增强。BPS/IC患者静息状态下血去甲肾上腺素水平和24小时尿样去甲肾上腺素水平较高。苯肾上腺素可增加内脏疼痛、脊髓Fos表达、膀胱反射活动、尿斑和排出粪便颗粒的数量。尿路上皮变薄，caspase3、bax免疫反应增强。台盼蓝染色仅在苯肾上腺素处理的动物中观察到。上皮下神经共表达α1和TRPV1。肥大细胞增多症存在于尿下层。膀胱炎增加了交感神经密度和尿去甲肾上腺素水平。结论过度的肾上腺素能刺激可能参与了BPS/IC的病理生理机制。诺鲁罗。乌罗代南。2015年34：489-496。(C)2013年威利期刊公司。
AimsTo evaluate sympathetic system activity in bladder pain syndrome/interstitial cystitis (BPS/IC) patients and to investigate if chronic adrenergic stimulation in intact rats induces BPS/IC-like bladder modifications. MethodsClinical studyIn BPS/IC patients and aged and body mass index matched volunteers TILT test was undertaken and catecholamines were measured in plasma and 24hr urine samples. Experimental studyPhenylephrine was injected subcutaneously (14 days) to female Wistar rats. Pain behavior, spinal Fos expression, urinary spotting, number of fecal pellets expelled, frequency of reflex bladder contractions, and urothelial height were analyzed. Urothelium permeability was investigated by trypan blue staining. Immunoreactivity against caspase 3 and bax were studied in the urothelium and against alpha-1-adrenoreceptor and TRPV1 in suburothelial nerves. Mast cell number was determined in the sub-urothelium. In rats with lipopolysaccharide-induced cystitis, urinary catecholamines, and Vesicular Monoamine Transporter 2 (VMAT2) expression in bladder nerves were analyzed. ResultsThe TILT test showed an increase of sympathetic activity. Noradrenaline levels in blood at resting conditions and in 24-hr urine samples were higher in BPS/IC patients. Phenylephrine administration increased visceral pain, spinal Fos expression, bladder reflex activity, urinary spotting and the number of expelled fecal pellets. The mucosa showed urothelial thinning and increased immunoreactivity for caspase 3 and bax. Trypan blue staining was only observed in phenylephrine treated animals. Suburothelial nerves co-expressed alpha1 and TRPV1. Mastocytosis was present in the suburothelium. Cystitis increased sympathetic nerve density and urinary noradrenaline levels. ConclusionsExcessive adrenergic stimulation of the bladder may contribute to the pathophysiological mechanisms of BPS/IC. Neurourol. Urodynam. 34:489-496, 2015. (c) 2013 Wiley Periodicals, Inc.