5-羟色胺类物质改善脊髓损伤排尿障碍的实验研究

项目名称： 5-羟色胺类物质改善脊髓损伤排尿障碍的实验研究

项目编号： No.30872568

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 武器工业

项目作者： 谷宝军

作者单位： 上海交通大学

项目金额： 31万元

中文摘要： 下尿路正常的储尿和排尿功能依赖于膀胱、尿道及尿道外括约肌的协同作用。逼尿肌-括约肌失协调导致的排尿障碍是骶髓以上水平脊髓损伤最常见的下尿路病变，也可能发生于脑血管意外、多发性硬化症、以及糖尿病神经病变等疾病。研究通过动物实验证实了5-羟色胺类物质对脊髓损伤及糖尿病导致的逼尿肌括约肌失协调有明确改善作用，并且筛选出了5-羟色胺受体中5-HT1A和5-HT7亚型的激动剂可以作用于脊髓中控制膀胱传出神经的骶髓副交感神经核以及控制尿道外扩约肌运动神经的Onuf's核内受体，从而改善排尿期膀胱逼尿肌和尿道括约肌的协调功能。即提高排尿效率、减少膀胱残余尿，从而降低膀胱内压、保护肾脏功能。为开发利用5-羟色胺类新药治疗改善逼尿肌-括约肌失协调提供了理论基础和动物实验证据。

中文关键词： 脊髓损伤；糖尿病；排尿障碍；尿道括约肌；5-羟色胺。

英文摘要： Storage and release of urine requires coordination between the urinary bladder and the external urethral sphincter (EUS). The voiding dysfunction by the detrusor-sphincter dyssynergia often happens in spinal cord injury patient, and also can be seen in the patient of the cerebrovascular accident, the multiple sclerosis, or the diabetic neuropathy. Our study, in the spinal cord injury or the diabetes mellitus animal models, proved serotonin, especially 5-HT1A receptor agonist and 5-HT7 receptor agonist could improve the detrusor-sphincter dyssynergia by acting the serotonin receptors in the lumbosacral parasympathetic nucleus, as well as in the sphincter motor nuclei (Onuf's nuclei), resulting from an increase in micturition volume, an decrease in residual volume and the improvement in voiding efficiency. These results may have implications for the future treatment of voiding dysfunction in the detrusor-sphincter dyssynergia patients.

英文关键词： spinal cord injury; diabetes mellitus; voiding dysfunction；urethral sphincter；serotonin.