K-2阿片受体激动剂诱发大鼠膀胱括约肌和尿道外括约肌失协调  

Bladder and External Urethral Sphincter Dyssynergia Induced byκ-2 Opioid Receptor Agonists in the Female Rat

作　　者：谷宝军[1] 刘峰[1] Zhongguang YANG 司捷旻[1] 徐月敏[1] 

机构地区：[1]上海交通大学附属第六人民医院泌尿外科,上海200233 [2]Department of Surgery,Division of Urology,Duke University Medical Center(Durham,North Carolina,USA)

出　　处：《临床泌尿外科杂志》2009年第8期624-626,630,共4页Journal of Clinical Urology

基　　金：国家自然科学基金资助项目(编号30872568);上海市科委启明星计划资助项目(编号04QMX1416)

摘　　要：目的:通过脊髓鞘内给与选择性κ-1(U-50,488)和κ-2(GR-89,696)阿片受体激动剂来验证脊髓κ阿片受体亚型在大鼠尿道外括约肌控制中的作用。方法:乌拉坦麻醉雌性大鼠,膀胱顶部插管充盈膀胱诱发排尿进行膀胱测压,肌电图评估尿道外括约肌(EUS)功能,脊髓鞘内或静脉注射给药。结果:大鼠排尿时EUS在基础的(连续的)收缩活动之上出现高频舒张收缩以利于排空尿道完成排尿。GR-89,696(0.05 to 5μg鞘内注射it)使EUS每次排尿时的舒张收缩的次数呈剂量依赖性减少。它使排尿效率降低,大剂量时导致EUS排尿时的舒张收缩消失,呈持续收缩状态,出现膀胱逼尿肌和EUS协同失调和充盈性尿失禁。非选择性阿片受体拮抗剂纳洛酮(1mg/kg静脉注射iv)可阻滞GR 89,696的效应。U-50,488(0.05 to 5g鞘内注射it)对膀胱内压和EUS肌电图参数无影响。结论:大鼠有效的排尿需要依靠脊髓信号发生器刺激EUS运动神经元产生信号,使EUS产生舒张收缩,从而导致尿道快速的舒张与收缩以利于排空。脊髓鞘内注射κ-2阿片受体激动剂可以抑制信号发生器,减少每次排尿期舒张收缩的次数,但并不影响与尿道关闭有关的基础收缩。由此产生膀胱逼尿肌和EUS协同失调,导致排尿效率降低。和大鼠脊髓损伤导致的膀胱逼尿肌和EUS协同失调排尿障碍相似。因此,应该进一步研究κ-2阿片受体在脊髓损伤导致的排尿障碍中的作用。Objective：To examine the role of spinal K-opioid receptor subtypes in the control of external ure thral sphincter （EUS） function in rats using selectivek-1 （U-50,488） or k-2 （GR-89,696） opiate receptor agonists. Methods：Urethane anesthetized female rats were catheterized through the bladder dome for cystometry. EUS func tion was assessed eleetromyographically. Drugs were administered intratheeally or intravenously. Results： Micturition in rats is accompanied at different times by tonic （continuous） EUS spike activity and by phasic bursts of spikes separated by pauses. GR 89,696 （0.05 to 5 ptg intrathecally） caused a dose dependent decrease in the num bet of bursts per micturition without affecting spike frequency within individual bursts or during periods of tonic activity. It resulted in decreased voiding efficiency. At high doses, it resulted the relaxation and contraction of EUS disappeared during the voiding and sustained contraction, bladder and external urethral sphincter dyssynergia and overflow incontinence. The nonselective opiate receptor antagonist naloxone （1 mg/kg intravenously） blocked GR-89,696 effects. U 50,488H （0.05 to 15 μg intrathecally） caused no change in cystometric parameters or in EUS-electromyography. Conclusions：Efficient voiding in rats depends on a spinal pattern generator causing EUS motor neuron firing to occur in bursts, resulting in rapid urethral contraction and relaxation. Intratheeal K-2-opiate receptor agonists suppress this pattern generator, decreasing the number of bursts occurring during each micturi- tion without decreasing motor neuron spike frequency during individual bursts or during tonic spike activity associ- ated with urethral closure. Resultant dyssynergia leads to decreased voiding efficiency. The relevance of K-2 opioid receptors should be explored in higher species, especially regarding spinal cord injury induced dyssynergia.

关 键 词：阿片受体 尿道 膀胱 脊髓 大鼠 

分 类 号：R322.62[医药卫生—人体解剖和组织胚胎学]