Kitta Takeya, Yoshikawa Satoru, Kawamorita Naoki, de Groat William C, Nonomura Katsuya, Yoshimura Naoki
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Neurourol Urodyn. 2016 Jan;35(1):122-7. doi: 10.1002/nau.22690. Epub 2014 Oct 30.
Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats.
Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method.
In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa.
These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.
压力性尿失禁（SUI）在绝经后女性中很常见。因此，本研究探讨了衰老和卵巢切除术（OVX）诱导的雌激素缺乏如何影响大鼠中防止喷嚏诱导性SUI的尿道控尿机制。
年轻（3个月大）和中年（12个月大）雌性大鼠接受双侧OVX或假手术。通过打喷嚏期间尿道反应的幅度（A-URS）和尿道基线压力（UBP）来测量尿道活动。采用TUNEL法检测尿道组织切片中的凋亡变化。
与年轻大鼠相比，中年大鼠的UBP显著降低，但A-URS没有显著降低。在3周龄的OVX大鼠中，年轻组和中年组的A-URS均比假手术大鼠显著降低，且OVX诱导的A-URS降低在中年大鼠中更明显。3周龄的年轻OVX大鼠和假手术大鼠在打喷嚏时均未漏尿；然而，在3周龄的中年OVX大鼠中有2/8发生了SUI，而在OVX 6周后，5/8的年轻大鼠和6/8的中年大鼠出现了SUI。在中年大鼠中，尿道横纹肌中的TUNEL阳性细胞显著增加，而在OVX后，黏膜中也发现阳性细胞数量增加。
这些结果表明，尽管在尿道横纹肌中发现了凋亡变化，但衰老比横纹肌介导的反射活动更易损害尿道基线功能。雌激素缺乏还会损害横纹肌介导的控尿反射。因此，衰老和雌激素缺乏以不同且累加的方式影响尿道基线功能以及神经诱发的、横纹肌介导的尿道控尿机制，从而诱发SUI。
