5-羟色胺1A受体激动剂改善脊髓损伤大鼠排尿功能障碍的实验研究

目的 研究5-羟色胺-1A(5-HTlA)受体激动剂对慢性脊髓损伤(spinal cord injury,SCI)大鼠排尿障碍的改善作用. 方法 雌性SD大鼠14只,体质量175 ～ 200 g.随机分为2组:实验组7只显微镜下大鼠T10棘突水平行脊髓离断建立脊髓损伤模型,正常对照组7只.8周后乌拉坦(1.3 g/kg)麻醉下,2组大鼠颈静脉和膀胱内置管,连接压力感受器,记录膀胱最大容量、残余尿量、排尿量和尿道外括约肌的肌电活动.静脉注入5-HTI A/7受体激动剂8-羟基-丙胺-四氢萘(8-OH-DPAT,0.03 ～1.00 mg/kg),得出剂量—效应曲线后再给予5HTIA受体抑制剂WAY-100635 (0.3g/kg).观察比较2组大鼠用药前后尿动力学指标的变化. 结果 随着8-OH-DPAT剂量增加,SCI大鼠膀胱容量从(33.2 ±8.3)ml降至(22.8±2.4) ml,排尿量从(0.14±0.08)ml增至(0.38 ±0.09) ml,残余尿量从(3.68±1.36)ml降至(1.84±0.21)ml,而膀胱最高压力从(27.1±3.6)mm Hg(1 mm Hg=0.133 kPa)降至(22.8±2.4) mm Hg,用药前后差异均有统计学意义(P＜0.05).对照组大鼠用药前后排尿情况变化差异无统计学意义.肌电图显示8-OH-DPAT引起SCI大鼠尿道外括约肌强直收缩中出现阶段性的松弛,正常对照组大鼠作用无明显改变. 结论 8-OH-DPAT可以剂量依赖性地部分恢复SCI大鼠的尿道外括约肌协调性松弛,从而降低膀胱容量,增加排尿量,减少残尿量,增加排尿效率,改善排尿障碍.

Improving the voding dysfunction by a 5-HT1A receptor agonist in rats with chronic spinal cord injury

Objective To investigate the effect of 5-hydroxytryptamine serotonin receptor-1A (5-HT1 A) agonists on micturition dysfunction in rats with chronic spinal cord injury (SCI).Methods Female SD rats weighing 175 -200 g were used.Seven of the rats were modified for a spinal cord injury model (transsection at T10).Eight weeks later,control rats and SCI rats were tested.Rats were anesthetized with urethane ( 1.3 g/kg ).A polyethylene (PE) -50 catheter was placed in the left jugular vein for intravenous drug administration.A PE-90 catheter was inserted through the bladder dome,and the other end of the bladder catheter was connected to a syringe pump for continuous infusion of saline and to a pressure transducer for intravesical pressure monitor.Dose-response curves for 8-OH-DPAT were followed by the WAY-100635 test.The capacity,residual volume,micturition volume,and EUS-EMG were measured.Results With an increasing dose of 8-OH-DPAT,the capacity of the bladder decreased from 33.2 ± 8.3 ml to 22.8 ± 2.4 ml.The micturition volume was increased from 0.14 ± 0.08 ml to 0.38 ± 0.09 ml.The residual volume decreased from 3.68 ± 1.36 ml to 1.84 ± 0.21 ml,and peak intravesical pressure changed from 27.1 ± 3.6 mm Hg to 22.8 ± 2.4 mm Hg.Control rats showed little significant change in the cystometric variable.Effects of 8-OH-DPAT were reversed by WAY-100635.That 8-OH-DPAT induced phasic relaxation occured in spinal cord-injured rats but the control group showed no significant change.Conclusions The 5-HTIA/7 receptor agonist 8-OH-DPAT may induce periodic EUS relaxation during voiding in urethane-anesthetized chronic spinal cordinjured rats.And this could result in an increase in micturition volume,a decrease in bladder capacity,and thus an increase in voiding efficiency.