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

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

目的研究5-羟色胺-1A（5-HTIA）受体激动剂对慢性脊髓损伤（spinalcordinjury，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—200g。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（1．3g／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-HTlA／7受体激动剂8-羟基-丙胺-四氢萘（8-OH—DPAT，0．03—1．00ms／kg），得出剂量-效应曲线后再给予5HTlA受体抑制剂WAY-100635（0．3s／ks）。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）mmHg（1mmHg=0．133kPa）降至（22．8±2．4）mmHg，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。

Objective To investigate the effect of 5-hydroxytryptamine serotonin receptor-1A （5- HT1A） 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 （transseetion 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 intravesieal pressure monitor. Dose-response curves for 8-OH-DPAT were followed by the WAY-100635 test. The capacity, residual volume, mieturition 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 mieturition 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- HT1 A/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.