Seidlová-Wuttke D, Schultens A, Jarry H, Wuttke W
Department of Clinical and Experimental Endocrinology, University of Goettingen, Germany.
Endocrine. 2004 Feb;23(1):25-32. doi: 10.1385/ENDO:23:1:25.
Whether estrogens have a beneficial effect in the urinary bladder to prevent or to delay occurrence of urinary bladder incontinence is an open question. Good animal models are missing. Therefore, in ovariectomized (ovx) rats we studied the effects of estradiol (E2) administered with food for 3 mo on urodynamic properties of the urinary bladder and the urethra. A biluminal catheter with one outlet in the bladder and another in the urethra in juxtaposition to the external sphincter was inserted in isoflurane anaesthetized animals. Within 2 x 30 s (1 min apart) 0.5 mL Ringer's solution was infused into the bladder and the inner vesicular and urethral pressure were recorded. In comparison to ovx estradiol-treated rats, ovx animals had significantly (p < 0.05) lower vesicular and urethral pressure. In the sham-treated ovx animals vesicular and urethral pressures were unstable and appeared uncoordinated, whereas estrogens increased vesicular and urethral pressure in a coordinated way, such that in these animals leaked volume was significantly lower than in the sham-treated ovx animals. By means of quantitative RT-PCR we demonstrate that the upper and lower part of the bladder and the urethra express estrogen receptor of the alpha- and beta-subtype (ER alpha and beta) and nerve growth factor, which is associated with painful sensations in inflamed urinary bladders. E2 downregulated both ERs in the bladder but not in the urethra, while NGF gene expression was downregulated in the urethra but unaffected by E2 in the bladder. It is concluded that estrogen deprivation causes uncoordinated function of the detrusor and sphincter muscles and that this effect can be prevented by estradiol.
雌激素在膀胱中是否具有预防或延迟膀胱失禁发生的有益作用仍是一个悬而未决的问题。目前尚缺乏良好的动物模型。因此,我们在去卵巢(ovx)大鼠中研究了连续3个月通过食物给予雌二醇(E2)对膀胱和尿道尿动力学特性的影响。在异氟烷麻醉的动物中插入一根双腔导管,其中一个出口位于膀胱,另一个出口位于与外括约肌相邻的尿道。在2×30秒(间隔1分钟)内,将0.5 mL林格氏液注入膀胱,并记录膀胱内压和尿道内压。与接受雌二醇治疗的去卵巢大鼠相比,去卵巢动物的膀胱内压和尿道内压显著较低(p<0.05)。在假手术处理的去卵巢动物中,膀胱内压和尿道内压不稳定且不协调,而雌激素以协调的方式增加膀胱内压和尿道内压,使得这些动物的漏尿量显著低于假手术处理的去卵巢动物。通过定量逆转录聚合酶链反应(RT-PCR),我们证明膀胱和尿道的上部和下部表达α和β亚型的雌激素受体(ERα和ERβ)以及神经生长因子,后者与炎症膀胱中的疼痛感觉有关。E2下调了膀胱中的两种雌激素受体,但未下调尿道中的雌激素受体,而神经生长因子(NGF)基因表达在尿道中被下调,但在膀胱中不受E2影响。结论是雌激素缺乏会导致逼尿肌和括约肌肌肉功能不协调,而这种影响可以通过雌二醇来预防。