Yoshida Junya, Aikawa Ken, Yoshimura Yasukuni, Shishido Keiichi, Yanagida Tomohiko, Yamaguchi Osamu
Department of Urology, Fukushima Medical University, Fukushima, Japan.
Neurourol Urodyn. 2007;26(7):1050-5. doi: 10.1002/nau.20438.
The present study investigated the effects of ovariectomy and estrogen replacement on the release of acetylcholine (Ach) from cholinergic neurons as well as on the tetrodotoxin (TTX)-insensitive stretch-induced Ach release in isolated rat detrusor. In addition, the above effects on rat micturition characteristics were also studied.
Thirty female rats randomly received a sham operation, ovariectomy, or ovariectomy plus estrogen replacement. Using metabolic cages, micturition parameters were recorded. Then, in vitro functional experiments that included the measurements of nerve-mediated detrusor muscle contraction, Ach release from nerve fibres, and stretch-induced TTX-insensitive Ach release were performed. Ach release was measured using microdialysis and high-performance liquid chromatography.
Ovariectomized rats showed a significant decrease in voided volume and significant increase in 24-hr frequency of voiding. Ovariectomy caused the significant increase in both TTX-insensitive basal Ach release and TTX-insensitive stretch-induced Ach release. On the other hand, ovariectomy caused a significant decrease in Ach release from nerve fibres, resulting in the decrease in the contractile responses of detrusor muscle to electrical nerve stimulation. Estrogen replacement restored these alterations induced by ovariectomy.
Our findings showed that as a results of estrogen deficiency, Ach release from nerve fibres decreased, suggesting that this reduction of Ach released from cholinergic nerves may cause the decrease in detrusor contractility. Furthermore, this study also demonstrated that stretch-induced TTX-insensitive Ach release was increased by ovariectomy. This may be a contributing factor to the development of overactive bladder in elderly women.
本研究调查了卵巢切除术及雌激素替代对胆碱能神经元乙酰胆碱（Ach）释放的影响，以及对离体大鼠逼尿肌中对河豚毒素（TTX）不敏感的牵张诱导Ach释放的影响。此外，还研究了上述影响对大鼠排尿特征的作用。
30只雌性大鼠随机接受假手术、卵巢切除术或卵巢切除术加雌激素替代。使用代谢笼记录排尿参数。然后，进行体外功能实验，包括测量神经介导的逼尿肌收缩、神经纤维释放Ach以及牵张诱导的对TTX不敏感的Ach释放。使用微透析和高效液相色谱法测量Ach释放。
去卵巢大鼠的排尿量显著减少，24小时排尿频率显著增加。卵巢切除术导致对TTX不敏感的基础Ach释放和对TTX不敏感的牵张诱导Ach释放均显著增加。另一方面，卵巢切除术导致神经纤维Ach释放显著减少，导致逼尿肌对电神经刺激的收缩反应降低。雌激素替代恢复了卵巢切除术引起的这些改变。
我们的研究结果表明，由于雌激素缺乏，神经纤维释放的Ach减少，这表明胆碱能神经释放的Ach减少可能导致逼尿肌收缩力下降。此外，本研究还表明，卵巢切除术增加了牵张诱导的对TTX不敏感的Ach释放。这可能是老年女性膀胱过度活动症发生的一个促成因素。
