中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 2093-2098.doi: 10.4103/1673-5374.308667

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

选择性5-羟色胺再摄取抑制剂氟西汀可改善中度脊髓损伤小鼠的膀胱功能

  

  • 出版日期:2021-10-15 发布日期:2021-03-19
  • 基金资助:

    江苏省中医院项目(Y19061

Fluoxetine, a selective serotonin reuptake inhibitor used clinically, improves bladder function in a mouse model of moderate spinal cord injury 

Long Ma1, #, Jing-Yuan Tang1, #, Jin-Yong Zhou2, Chen Zhu1, Xin Zhang1, Ping Zhou1, Qiu Yu1, Yan Wang1, Xiao-Jian Gu1, *#br#   

  1. 1Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China; 2Department of Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Xiao-Jian Gu, guxj61@hotmail.com.
  • Supported by:
    This work was supported by Jiangsu Province Hospital of Chinese Medicine, No. Y19061 (to LM). 

摘要:

脊髓损伤后,脊髓向上传导丧失,使患者丧失对排尿的控制,表现为逼尿肌-括约肌协同失调以及排尿不足。有研究显示5-羟色胺能轴突在控制排尿功能的下行束方面起重要作用。实验建立了中度脊髓挫伤模型下小鼠,伤后35d使用5-羟色胺能激动剂喹哌嗪 (0.2 mg/kg)、8-羟基-2-(二丙基氨基)四氢萘氢溴酸盐0.1 mg / kg)、丁螺环酮 (1mg / kg)、舒马曲坦(1 mg / kg)和利扎曲坦(50 mg / kg)、5-羟色胺再摄取抑制剂氟西汀(20 mg / kg)和度洛西汀(1mg / kg)以及多巴胺受体激动剂SKF-82197(0.1 mg / kg)腹腔注射进行治疗。以尿斑测定和尿动力学检测显示,氟西汀可明显减少中度脊髓挫伤小鼠残余尿量,降低膀胱和尿道括约肌压力,但氟西汀也不能改善重度脊髓脊髓挫伤小鼠的排尿功能,而其他5-羟色胺能药物则对小鼠的排尿功能没有影响。实验于2020年9月11日经江苏省中医院伦理委员会批准,批准号2020DW-20-02。

https://orcid.org/0000-0002-8733-0269 (Xiao-Jian Gu)

关键词:

氟西汀, 脊髓损伤, 膀胱, 排尿, 5-羟色胺再摄取抑制剂, 尿动力学, 尿斑, 尿道外括约肌

Abstract: After spinal cord injury, the upward conduction of the spinal cord is lost, resulting in the loss of micturition control, which manifests as detrusor sphincter dyssynergia and insufficient micturition. Studies have shown that serotonergic axons play important roles in the control of the descending urination tract. In this study, mouse models of moderate spinal cord contusions were established. The serotonin agonists quipazine (0.2 mg/kg), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DAPT, 0.1 mg/kg), buspirone (1 mg/kg), sumatriptan (1 mg/kg), and rizatriptan (50 mg/kg), the serotonin reuptake inhibitors fluoxetine (20 mg/kg) and duloxetine (1 mg/kg), and the dopamine receptor agonist SKF-82197 (0.1 mg/kg) were intraperitoneally administered to the model mice 35 days post-injury in an acute manner. The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury. However, fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury. In contrast, the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice. This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine (approval No. 2020DW-20-02) on September 11, 2020.

Key words: bladder, external urethral sphincter, fluoxetine, micturition, selective serotonin reuptake inhibitor, spinal cord injury, urodynamics, voided stain on paper measurement 

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