电刺激联合吊带术治疗女性压力性尿失禁的实验研究

Stress urinary incontinence (SUI) is a common medical condition for women with severe social burdens. The number of SUI patients has grown considerably over the past decades due to the aging people is growing rapidly. The mid-urethral sling procedure has gained widespread popularity and has high success rate, however, the complete mechanism of this procedure for SUI remains unclear. Up to one third women will undergo a second anti-SUI surgery due to recurrent SUI during their lifetime. SUI with intrinsic sphincter deficiency (ISD) is predictive of lower rates of dryness after mid-urethral sling treatment. Electrical stimulation is a well-established clinical strategy to augment muscle performance. Moreover, electrical stimulation can increase brain-derived neurotrophic factor (BDNF) expression in injured neurons, activate Schwann cells, and promote neuroregeneration after nerve injury. Therefore, we hypothesis that electrical stimulation using electrical wires embedded in the sling mesh may improve contraction of periurethral muscles and prevent sling failures and recurrent SUI. In this study, with our newly developed electrical wires embedded sling mesh, we will establish a dual muscle and nerve injury SUI animal model in order to test the mechanism of electrical stimulation with sling placement for the treatment of SUI models.

压力性尿失禁(stress urinary incontinence, SUI)是女性患者的常见疾病且严重困扰女性健康。在我国由于人口老龄化的加速，SUI的发病率呈明显上升趋势。中段尿道吊带手术因其成功率高而得到广泛推广，而其治疗SUI的确切机制仍不明晰。超过三分之一的女性患者出现复发而需要接受第二次抵抗SUI手术。SUI患者通常同时伴有不同程度的固有括约肌缺陷和尿道支撑缺损。而电刺激一方面可以用来改善肌肉的收缩功能，另一方面还可以提高受损神经元中脑源性神经营养因子的表达量，激活Schwann细胞，促进神经肌肉接头的恢复。因而，我们提出假设利用植入吊带内的电极，中段尿道吊带术后联合电刺激可以预防SUI手术失败和复发。本实验研究拟通过建立神经-肌肉双重损伤SUI大鼠模型，利用创新设计的电极植入吊带，使用电刺激联合吊带手术治疗SUI大鼠的控尿功能，并阐明该方法治疗SUI的分子及神经生理学机制。

本研究通过构建神经-肌肉双重损伤压力性尿失禁（SUI）大鼠模型，制备电极埋入吊带并将其放置在大鼠中段尿道位置，从而使得大鼠尿道外括约肌得到支撑并在电刺激下充分收缩以对抗腹压升高所引起的漏尿。然后通过测定不同电刺激参数（频率，脉冲持续时间，电流强度）对SUI大鼠漏尿点压力的影响，确定最佳的参数组合为后续进一步实验提供依据。利用之前确定的电刺激参数组合，在正常大鼠和SUI损伤大鼠中测定电极植入吊带放置在尿道中段位置后，电刺激联合吊带手术对漏尿点压力，尿道外括约肌肌电图，阴部神经电位的影响，以阐明该方法治疗SUI的神经生理学机制。通过以上研究的开展，我们发现电刺激联合吊带手术成功使得尿失禁大鼠的漏尿点压力显著升高，而该过程的发生主要依赖于脑源性神经营养因子的表达，该研究为SUI的治疗方案提供了新的思路，并有望在未来通过转化应用于临床实际。