宫内膀胱流出道梗阻对胎羊逼尿肌收缩性、顺应性及神经支配的影响。

Effects of in utero bladder outflow obstruction on fetal sheep detrusor contractility, compliance and innervation.

作者信息

Nyirady Peter, Thiruchelvam Nikesh, Fry Christopher H, Godley Margaret L, Winyard Paul J D, Peebles Donald M, Woolf Adrian S, Cuckow Peter M

机构信息

Nephro-Urology Unit, Institute of Child Health, University College, London, United Kingdom.

出版信息

J Urol. 2002 Oct;168(4 Pt 1):1615-20. doi: 10.1016/S0022-5347(05)64530-2.

DOI:10.1016/S0022-5347(05)64530-2

PMID:12352467

Abstract

PURPOSE

Congenital bladder outflow obstruction caused by posterior urethral valves is a common cause of end stage renal failure in boys. We hypothesized that fetal bladder outflow obstruction perturbs detrusor contractility and innervation and bladder storage volume-pressure relationships.

MATERIALS AND METHODS

Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery, when urinary tract dilatation, enlarged bladders and histologically abnormal kidneys were documented. Isolated strips of bladder detrusor from sham operated and obstructed fetuses were subjected to electrical field stimulation, carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Whole bladder storage characteristics were determined by filling cystometry and bladder innervation was investigated by immunohistochemistry and Western blot.

RESULTS

Tension-frequency contractility studies showed that obstructed fetal bladder strips were significantly hypocontractile versus sham operated controls in response to electrical field stimulation and the specific agonists carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Hypocontractility was greater with nerve mediated stimulation than with carbachol, suggesting relative denervation. Reduced innervation was confirmed by S100 and protein gene product 9.5 immunohistochemistry and by measuring a significant reduction in protein gene product 9.5 protein expression using Western blot. Filling cystometry showed that obstructed fetal bladders appeared more compliant (Delta V/Delta P, where Delta V is the change in volume and Delta P is the change in pressure) with larger capacity, more flaccidity and yet retained stress relaxation.

CONCLUSIONS

In response to severe experimental fetal bladder outflow obstruction the bladder becomes large and hypocontractile, and has aberrant innervation.

摘要

目的

后尿道瓣膜引起的先天性膀胱流出道梗阻是男孩终末期肾衰竭的常见原因。我们推测胎儿膀胱流出道梗阻会扰乱逼尿肌收缩力、神经支配以及膀胱储尿容量-压力关系。

材料与方法

在妊娠75天即妊娠中期通过放置尿道环和结扎脐尿管诱导雄性胎羊出现严重膀胱流出道梗阻。术后30天检查胎儿，记录尿路扩张、膀胱增大以及组织学异常的肾脏情况。对假手术和梗阻胎儿的膀胱逼尿肌分离条进行电场刺激、卡巴胆碱、氯化钾和α-β亚甲基三磷酸腺苷处理。通过充盈膀胱测压法确定整个膀胱的储尿特征，并通过免疫组织化学和蛋白质免疫印迹法研究膀胱神经支配。

结果

张力-频率收缩力研究表明，与假手术对照组相比，梗阻胎儿的膀胱条对电场刺激以及特异性激动剂卡巴胆碱、氯化钾和α-β亚甲基三磷酸腺苷的反应明显收缩力减弱。神经介导刺激引起的收缩力减弱比卡巴胆碱引起的更明显，提示相对去神经支配。通过S100和蛋白质基因产物9.5免疫组织化学以及使用蛋白质免疫印迹法测量蛋白质基因产物9.5蛋白表达显著降低，证实了神经支配减少。充盈膀胱测压法显示，梗阻胎儿的膀胱表现出更顺应性（ΔV/ΔP，其中ΔV是体积变化，ΔP是压力变化），容量更大，更松弛，但仍保留应力松弛。