Li Suning, Hydery Tasmina, Juan Yungshun, Lin Wei-Yu, Kogan Barry, Mannikarottu Anita, Leggett Robert E, Schuler Catherine, Levin Robert M
Albany College of Pharmacy, Albany, NY 12203, USA.
Urology. 2009 Sep;74(3):691-6. doi: 10.1016/j.urology.2009.02.068. Epub 2009 Jun 7.
To evaluate the effect ovariectomy (OVX) after 2 and 4 weeks on bladder function and biochemistry of the adult female rabbit urinary bladder.
Twelve mature female rabbits were divided into 3 groups: control, 2-week ovariectomized, and 4-week ovariectomized. At the end of the experimental period, the following studies were performed: contractile studies on isolated strips; examinations of the activity of citrate synthase (a marker for mitochondrial function) and thapsigargin-sensitive calcium ATPase (a marker for sarcoplasmic reticular calcium uptake function); and quantification of Rho-kinase (ROK) alpha and beta and myosin light chain kinase by Western blot analyses.
By 28 days after OVX, there were significant decreases in bladder weight, contractile responses, and citrate synthase and sarcoplasmic reticular calcium uptake activity. In addition, by 28 days following OVX the relative concentration of ROK alpha was significantly increased, whereas ROK beta concentration was significantly decreased. Myosin light chain kinase was significantly reduced.
Our study demonstrated that OVX contributed significantly to chronically decreased contractile function in the detrusor muscle of the female rabbit bladder, and this decrease, in turn, was mediated by decreased mitochondrial and sarcoplasmic reticulum function. These specific bladder dysfunctions could be related to the demonstrated decreased blood flow to the bladder muscle and mucosa and the increased generation of free radicals. Changes in smooth muscle regulatory proteins, especially myosin light chain kinase, may also play a role in contractile dysfunctions.
评估成年雌性兔在卵巢切除术后2周和4周时对膀胱功能及膀胱生化指标的影响。
将12只成年雌性兔分为3组:对照组、卵巢切除术后2周组和卵巢切除术后4周组。在实验期结束时,进行了以下研究:对离体膀胱条进行收缩性研究;检测柠檬酸合酶(线粒体功能标志物)和毒胡萝卜素敏感的钙ATP酶(肌浆网钙摄取功能标志物)的活性;通过蛋白质免疫印迹分析对Rho激酶(ROK)α和β以及肌球蛋白轻链激酶进行定量分析。
卵巢切除术后28天,膀胱重量、收缩反应以及柠檬酸合酶和肌浆网钙摄取活性均显著降低。此外,卵巢切除术后28天,ROKα的相对浓度显著升高,而ROKβ的浓度显著降低。肌球蛋白轻链激酶显著减少。
我们的研究表明,卵巢切除术对雌性兔膀胱逼尿肌的收缩功能长期下降有显著影响,而这种下降反过来又由线粒体和肌浆网功能降低所介导。这些特定的膀胱功能障碍可能与已证实的膀胱肌肉和黏膜血流减少以及自由基生成增加有关。平滑肌调节蛋白的变化,尤其是肌球蛋白轻链激酶,可能也在收缩功能障碍中起作用。