Chen Qin, Takahashi Satoru, Zhong Shan, Hosoda Chihiro, Zheng Huai-Ying, Ogushi Tetsuo, Fujimura Tetsuya, Ohta Nobutaka, Tanoue Akito, Tsujimoto Gozoh, Kitamura Tadaichi
Department of Urology, Faculty of Medicine, University of Tokyo, Japan.
J Urol. 2005 Jul;174(1):370-4. doi: 10.1097/01.ju.0000161210.17365.cc.
alpha1-Adrenoceptor (AR) blockers are known to relieve not only voiding symptoms, but also storage symptoms in elderly men. We investigated lower urinary tract function in mice lacking alpha1d-AR using frequency/volume analysis and filling cystometry.
A total of 10, 12-week-old female alpha1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were studied. Each mouse was placed in a metabolic cage connected to a digital scale and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency and volume were recorded for 48 hours. After frequency/volume analysis filling cystometry was performed with the mice awake and without restraint. The expression of alpha1-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction.
Mean daily voiding frequency +/- SD in alpha1d-KO mice was 9.0 +/- 2.1, significantly lower than 15.9 +/- 5.2 in WT mice (p = 0.0048). Mean volume per void in alpha1d-KO mice was significantly larger than in WT mice (0.24 +/- 0.02 vs 0.16 +/- 0.03 ml, p = 0.0096). Similarly cystometric analysis demonstrated larger bladder capacity (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in alpha1d-KO mice compared with those in WT mice. No significant difference in maximum pressure at void was observed between the 2 groups. In WT mice the amount of alpha1a, alpha1b and alpha1d-AR subtype mRNA in the bladder was 5.2 +/- 0.7, 1.0 +/- 0.1 and 6.3 +/- 0.7 gene copies per ng total RNA, respectively. In contrast, alpha1d-AR transcript was not detectable in alpha1d-KO mice but alpha1a and alpha1b-AR expression was similar to that in WT mice.
The results demonstrate that the alpha1d-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that alpha1-blockers with significant affinity for alpha1d-AR are effective for treating storage symptoms associated with benign prostatic obstruction.
已知α1肾上腺素能受体（AR）阻滞剂不仅可缓解老年男性的排尿症状，还可缓解其储尿症状。我们使用频率/容量分析和充盈性膀胱测压法研究了缺乏α1d-AR的小鼠的下尿路功能。
共研究了10只12周龄的雌性α1d基因敲除（KO）小鼠和10只年龄匹配的雌性野生型（WT）小鼠。将每只小鼠置于连接有数字秤和个人计算机的代谢笼中。在12/12小时明暗循环条件下，记录48小时的排尿频率和尿量。在进行频率/容量分析后，在小鼠清醒且无约束的状态下进行充盈性膀胱测压。使用实时聚合酶链反应对每组小鼠膀胱中α1-AR亚型mRNA的表达进行定量分析。
α1d-KO小鼠的平均每日排尿频率±标准差为9.0±2.1，显著低于WT小鼠的15.9±5.2（p = 0.0048）。α1d-KO小鼠每次排尿的平均尿量显著大于WT小鼠（0.24±0.02 vs 0.16±0.03 ml，p = 0.0096）。同样，膀胱测压分析显示，与WT小鼠相比，α1d-KO小鼠的膀胱容量更大（140%，p = 0.0008），排尿量更大（146%，p = 0.0048）。两组间排尿时的最大压力无显著差异。在WT小鼠中，膀胱中α1a、α1b和α1d-AR亚型mRNA的量分别为每纳克总RNA 5.2±0.7、1.0±0.1和6.3±0.7个基因拷贝。相比之下，在α1d-KO小鼠中未检测到α1d-AR转录本，但α1a和α1b-AR的表达与WT小鼠相似。
结果表明，α1d-AR亚型在调节膀胱功能中起重要作用。从理论上支持了一项临床发现，即对α1d-AR具有显著亲和力的α1阻滞剂可有效治疗与良性前列腺梗阻相关的储尿症状。
