The Effect of the 5-HT2A/2C Receptor Agonist DOI on Micturition in Rats with Chronic Spinal Cord Injury
The Effect of the 5-HT2A/2C Receptor Agonist DOI on Micturition in Rats with Chronic Spinal Cord Injury
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DOI：
10.1016/j.juro.2012.11.049
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发表时间：
2013-05-01
影响因子：
6.6
通讯作者：
Andersson, Karl-Erik
中科院分区：
文献类型：
--
作者：
Chen, Jiasheng;Gu, Baojun;Andersson, Karl-Erik
用途：本实验观察了5-HT_（2A）/_（2C）受体激动剂DOI对慢性脊髓损伤大鼠排尿功能的影响。在T10节段横断造成脊髓损伤。在横断后8至12周进行膀胱测压研究。使用乌拉坦麻醉对所有大鼠进行膀胱测压。选择性5-HT 2A拮抗剂酮色林给药后，每个DOI剂量-反应曲线。结果：与对照组相比，脊髓损伤组大鼠膀胱容量、排尿后残余尿量明显增加，排尿效率明显降低。在脊髓损伤大鼠中，DOI（0.01至0.3 mg/kg）诱导排尿量的显著剂量依赖性增加和残余量的减少，导致排尿效率增加。膀胱测压图测量显示高频振荡活动呈剂量依赖性增加，明显表现为每次排尿的小振荡次数增加。这与改善的空隙效率相关。Ketanserin（0.1 mg/kg）部分或完全逆转DOI诱导的changes.Conclusions：高频振荡似乎反映了排尿过程中的外尿道括约肌爆发活动。脊髓损伤大鼠膀胱排尿效率和高频振荡活动降低。5-HT 2A受体激动剂可增强高频振荡活性，提高排尿效率。据我们所知，这些结果是否对脊髓损伤患者排尿功能障碍的未来治疗有意义还有待研究。
Purpose: We examined the effects of the 5-HT2A/2C receptor agonist DOI on micturition in chronic spinal cord injured rats.Materials and Methods: Female Sprague-Dawley (R) rats were used. Spinal cord injury was produced by transection at the T10 level. A cystometric study was performed 8 to 12 weeks after transection. Cystometrograms were done using urethane anesthesia in all rats. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve. All drugs were administered intravenously.Results: Compared to controls, spinal cord injured rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. In spinal cord injured rats DOI (0.01 to 0.3 mg/kg) induced significant dose dependent increases in micturition volume and decreases in residual volume, resulting in increased voiding efficiency. Cystometrogram measurements showed a dose dependent increase in high frequency oscillation activity, evident as an increased number of small oscillation per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI induced changes.Conclusions: High frequency oscillation seems to reflect external urethral sphincter burst activity during voiding. Bladder voiding efficiency and high frequency oscillation activity were decreased in spinal cord injured rats. High frequency oscillation activity can be enhanced by 5-HT2A receptor agonism, improving voiding efficiency. To our knowledge it remains to be studied whether these results may have implications for the future treatment of voiding dysfunction in patients with spinal cord injury.