血管紧张素Ⅱ受体拮抗剂替米沙坦对膀胱出口梗阻大鼠逼尿肌过度活动的影响。
Effect of angiotensin II receptor antagonist telmisartan on detrusor overactivity in rats with bladder outlet obstruction.
机构信息
Department of Urology, College of Medicine, Hallym University, Seoul, Korea.
出版信息
Urology. 2012 Nov;80(5):1163.e1-7. doi: 10.1016/j.urology.2012.05.002. Epub 2012 Jul 13.
OBJECTIVE
To investigate the changes of expression in both the nerve growth factor (NGF) and the angiotensin II type 1 (AT1) receptors in the urothelium and the detrusor muscle in a rat model of bladder outlet obstruction (BOO). To determine whether the AT1 receptor antagonist telmisartan alleviated the detrusor overactivity in rats with BOO.
METHODS
Male Sprague-Dawley rats were randomly assigned to 3 groups. The control group (n = 10) was sham-operated. The animals in the BOO (n = 20) and the telmisartan groups (n = 20) underwent a partial BOO operation. The telmisartan group received telmisartan (3 mg/kg/d) for 14 days. Cystometry was performed in all 3 groups for 2 weeks after surgery. The expression levels and the cellular distribution of NGF and AT1 receptors were quantified by Western blot analysis and immunofluorescence staining.
RESULTS
On cystometry, the intercontraction interval was shorter and the mean number of nonvoiding contractions was increased in the BOO group, compared with those in the control group. The intercontraction interval was longer and the number of nonvoiding contractions was reduced in the telmisartan group, compared with those in the BOO group. In Western blotting and immunofluorescence staining, we found that the expression and the immunoreactivity of NGF and the AT1 receptors were increased in the BOO group, compared with those in the control group. However, with oral administration of telmisartan, those of NGF and AT1 were decreased.
CONCLUSION
The AT1 receptors may play a significant role in the pathogenesis of the detrusor overactivity in a rat model of BOO.
目的
研究神经生长因子（NGF）和血管紧张素 II 型 1 型受体（AT1）在膀胱出口梗阻（BOO）大鼠模型中的尿路上皮和逼尿肌表达变化。确定 AT1 受体拮抗剂替米沙坦是否能缓解 BOO 大鼠的逼尿肌过度活动。
方法
雄性 Sprague-Dawley 大鼠随机分为 3 组。对照组（n = 10）行假手术。BOO 组（n = 20）和替米沙坦组（n = 20）行部分 BOO 手术。替米沙坦组术后 14 天给予替米沙坦（3mg/kg/d）。所有 3 组术后 2 周行膀胱测压。通过 Western blot 分析和免疫荧光染色定量测定 NGF 和 AT1 受体的表达水平和细胞分布。
结果
在膀胱测压中，与对照组相比，BOO 组的收缩间期更短，非排尿收缩次数更多。与 BOO 组相比，替米沙坦组的收缩间期更长，非排尿收缩次数减少。在 Western blot 和免疫荧光染色中，我们发现 NGF 和 AT1 受体的表达和免疫反应性在 BOO 组中增加，而在对照组中则减少。然而，替米沙坦口服给药后，NGF 和 AT1 的表达减少。
结论
在 BOO 大鼠模型中，AT1 受体可能在逼尿肌过度活动的发病机制中起重要作用。
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