Oshiro Takuma, Miyazato Minoru, Saito Seiichi
Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Life Sci. 2014 Oct 22;116(1):37-42. doi: 10.1016/j.lfs.2014.08.009. Epub 2014 Aug 20.
To confirm the mechanisms of age-associated detrusor underactivity (DU), we examined the differences in bladder activity and connexin-43 (Cx43)-derived gap junctions in the bladders of young and old rats.
Female Sprague-Dawley rats aged 3months (young) and 12months (old) were used. Continuous cystometry was performed under urethane anesthesia in both ages of rats. In addition, isovolumetric cystometry was performed in young rats during the intravesical application of carbenoxolone, a gap junction blocker, to confirm the role of gap junction proteins in the bladder. Western blotting analyses were performed to assess Cx43 protein expression in the bladders of both groups of rats. Bladders were also analyzed using Masson's trichrome staining and immunostaining for Cx43.
Cystometric evaluations revealed that compared with young rats, bladder contractility was reduced by 27% and residual urine volume was significantly increased in old rats. However, the intercontraction intervals did not differ between the two groups. Under isovolumetric conditions, bladder contraction was suppressed after the intravesical application of carbenoxolone. In the bladders of old rats, increase of smooth muscle cell hypertrophy and fibrous tissue was observed compared with young rats. In association with these findings, immunostaining for smooth muscle Cx43 and its protein level were decreased by 28% compared with young rats.
These results suggest that age-related DU might be caused by the downregulation of gap junctional intercellular communication in the bladder. Consequently, the normal signals that contribute to voiding function might not be transported between detrusor muscles.
为了确定年龄相关性逼尿肌功能减退（DU）的机制，我们研究了年轻和老年大鼠膀胱活动及连接蛋白43（Cx43）衍生的缝隙连接的差异。
使用3个月龄（年轻）和12个月龄（老年）的雌性Sprague-Dawley大鼠。在两种年龄的大鼠中，于氨基甲酸乙酯麻醉下进行连续膀胱测压。此外，在年轻大鼠膀胱内应用缝隙连接阻滞剂生胃酮期间进行等容膀胱测压，以确认缝隙连接蛋白在膀胱中的作用。进行蛋白质免疫印迹分析以评估两组大鼠膀胱中Cx43蛋白的表达。还使用Masson三色染色和Cx43免疫染色对膀胱进行分析。
膀胱测压评估显示，与年轻大鼠相比，老年大鼠膀胱收缩力降低了27%，残余尿量显著增加。然而，两组之间的收缩间期无差异。在等容条件下，膀胱内应用生胃酮后膀胱收缩受到抑制。与年轻大鼠相比，老年大鼠膀胱中观察到平滑肌细胞肥大和纤维组织增加。与这些发现相关，与年轻大鼠相比，平滑肌Cx43的免疫染色及其蛋白水平降低了28%。
这些结果表明，年龄相关性DU可能是由膀胱中间隙连接细胞间通讯的下调引起的。因此，有助于排尿功能的正常信号可能无法在逼尿肌之间传递。
