Improving the voiding disfunction by a 5-HT2A receptor agonist in rats with chronic spinal cord injury
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摘要: 目的:研究5羟色胺-2A(5-HT2A)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:体重175~200 gSD雌性大鼠14只。随机分为两组:实验组7只,建立脊髓损伤模型;正常对照组7只。8周后乌拉坦麻醉下,在正常大鼠和SCI大鼠颈静脉和膀胱内置管,连接压力感受器,记录大鼠膀胱内压图(cystometrogram, CMG)及排尿量、剩余尿量、膀胱容量。静脉注入5-HT2A受体激动剂DOI(0.01~0.3 mg/kg),得到剂量-效应曲线后再给予5-HT2A受体抑制剂酮色林(ketanserin,0.1 mg/kg)。结果:对照组正常大鼠用药前后排尿量、膀胱容量下降,而大鼠排尿效率的差异无统计学意义。DOI能增加SCI大鼠排尿量,同时降低剩余尿量、膀胱容量,从而提高排尿效率,且效应随着DOI剂量增加而增加,差异有统计学意义。酮色林注入后能逆转DOI的作用。同时DOI能增加大鼠排尿时CMG中高频振动波(HFOs)活动,改善SCI大鼠尿道外括约肌高频舒张收缩功能,而对脊髓完好的正常大鼠作用微弱。结论:5-HT2A受体激动剂DOI可以剂量依赖性地增强SCI大鼠排尿时尿道外括约肌高频舒张收缩,从而增加排尿量,减少剩余尿量,降低膀胱容量,提高排尿效率,改善排尿障碍。Abstract: Objective: To investigate the effect of 5-hydroxytryptamine serotonin receptor-2A agonists on micturition dysfunction in rats with chronic spinal cord injury(SCI).Method: Female SD rats with the weight of 175-200g weight were used. Seven of these rats were made into the spinal cord injury model. 8 weeks later, control ras and SCI rats were tested. Rats were anesthetized with urethane. Control rats and SCI rats were catheterized through the bladder dome for saline-filling cystometry. Dose-response curves for iv DOI were followed by ketanserin test. The capacity, residual volume, micturition volume and voiding pressure were measured.Result: Intact rats showed few significant changes in cystometric variable. SCI rats responded to DOI with dose-dependent increase in micturition volume and decrease in capacity, residual volume and voiding pressure, resulting in improvement in voiding efficiency. Effects of DOI were reversed by ketanserin. That DOI facilitated EUS bursting activity in spinal cord injured rats but the control group showed no significant change.Conclusion: The 5-HT2A receptor agonist DOI may significantly enhance EUS bursting activity during voiding in urethane-anesthetized chronic spinal cord injured rats. And this could result in an increase in micturition volume, a decrease in bladder capacity, and thus an increase in voiding efficiency.
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Key words:
- spinal cord injury /
- urethral dysfunction /
- serotonin receptor /
- rat
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