Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder
Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder
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DOI：
10.5213/inj.2012.16.1.13
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发表时间：
2012-03-01
影响因子：
2.3
通讯作者：
Ko, Il-Gyu
中科院分区：
文献类型：
--
作者：
Kim, Sung-Eun;Shin, Mal-Soon;Ko, Il-Gyu
目的：膀胱过度活动症(OAB)以尿急为特征，常伴有尿频和夜尿。坦索罗辛是一种α(1)-肾上腺素能受体拮抗剂，广泛用于减轻尿路梗阻和前列腺增生症的症状。坦索罗辛可以穿过血脑屏障。方法：成年雌性SD大鼠，体重250+/-10g(9周龄)，实验动物为成年雌性SD大鼠。实验动物分为5组(每组8只)：对照组、OAB诱导组、OAB诱导+0.01 mg/kg坦索罗辛治疗组、OAB诱导+0.1 mg/kg坦索罗辛治疗组、OAB诱导+1 mg/kg坦索罗辛治疗组。环磷酰胺(75 mg/kg)每3d腹腔注射1次，共10d，诱导OAB。坦索罗辛治疗组大鼠口服坦索罗辛，每日1次，连续给药14d，从OAB诱导后1d开始。采用膀胱测压、c-Fos免疫组织化学、神经元性排尿中心一氧化氮合酶(NOS)-黄递酶组织化学和蛋白印迹法检测膀胱压力。结果：环磷酰胺注射后收缩压力增加，收缩时间延长，表现为OAB的诱导。坦索罗辛可显著抑制心肌收缩压力和收缩时间。OAB诱导的神经元排尿中心c-Fos和NOS表达增强。坦索罗辛可抑制OAB诱导的c-Fos和NOS的表达。结论：坦索罗辛对OAB诱导的神经元排尿中枢神经元激活有抑制作用。本研究结果提示坦索罗辛可能是改善OAB症状的有效治疗手段。
Purpose: The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, alpha(1)-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.Methods: Adult female Sprague-Dawley rats, weighing 250 +/- 10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.Results: Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.Conclusions: Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.