Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: Evidence in ovariectomized rodents
Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: Evidence in ovariectomized rodents
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DOI：
10.1016/s0022-5347(05)65935-6
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发表时间：
2001-09-01
影响因子：
6.6
通讯作者：
Kuchel, GA
中科院分区：
文献类型：
--
作者：
Zhu, Q;Ritchie, J;Kuchel, GA
目的：尽管逼尿肌多动伴收缩功能受损是老年患者常见的尿动力学表现，但据我们所知，其发病机制尚不清楚。活检研究表明，逼尿肌过度活动和收缩功能受损的受试者分别在孤立的逼尿肌过度活动和收缩功能受损的情况下有连接异常和退行性改变的超微结构证据。根据已知的雌激素对细胞的影响，我们推测卵巢激素分泌减少可能参与逼尿肌过度活动并伴有收缩功能受损的发病机制。材料和方法：成年13~14个月龄雌性Fisher 344大鼠双侧卵巢切除或假手术后4个月。结果：双侧卵巢切除后，逼尿肌收缩力减少25%，有核肌群减少12%，大量轴突退行性改变。双侧卵巢切除动物的肌条对卡巴胆碱产生的张力比同等大小的假手术动物的肌条少40%~50%，而M受体亲和力没有明显变化。结论：双侧卵巢切除导致了变性超微结构的许多改变，但没有表现出连接异常的特征。我们的结果表明，成熟的啮齿动物逼尿肌及其神经对长时间的卵巢激素缺乏敏感，从而导致啮齿动物的收缩能力受损。未来的研究需要确定雌激素是否在人类的变性超微结构模式或收缩能力受损中发挥作用。
Purpose: Although detrusor hyperactivity with impaired contractility is a common urodynamic finding in elderly subjects, to our knowledge its pathogenesis remains unknown. Biopsy studies indicate that subjects with detrusor hyperactivity and impaired contractility have ultrastructural evidence of dysjunction and degeneration patterns in isolated detrusor hyperactivity and impaired contractility, respectively. Based on the known cellular effects of estrogen we postulated that declines in ovarian hormone production may contribute to the pathogenesis of detrusor hyperactivity with impaired contractility.Materials and Methods: Mature 13 to 14-month-old female Fisher 344 rats were studied 4 months after bilateral ovariectomy or sham surgery. Detrusor structure was evaluated by electron microscopy and contractility was evaluated by muscle strip studies.Results: After bilateral ovariectomy detrusor smooth muscle decreased by 25% with a 12% decrease in the number of nucleated muscle profiles and degenerative changes in many axons. Muscle strips from bilaterally ovariectomized animals generated 40% to 50% less tension per strip in response to carbachol than strips of equal size from sham operated animals with no apparent change in muscarinic receptor affinity.Conclusions: Bilateral ovariectomy resulted in many changes of the degeneration ultrastructural pattern but in none of the characteristic features of the dysjunction pattern. Our results indicate that the mature rodent detrusor and its innervation are sensitive to prolonged ovarian hormonal deficiency, contributing to impaired contractility in rodents. Future studies are required to establish whether estrogen has a role in the degeneration ultrastructural pattern or impaired contractility in humans.