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新型选择性β-肾上腺素受体激动剂维贝格隆对帕金森病大鼠模型膀胱和尿道功能的影响。

Effects of a new selective β -adrenoceptor agonist, vibegron, on bladder and urethral function in a rat model of Parkinson's disease.

机构信息

Department of Renal and Genitourinary Surgery, Graduate School of Medical Science, Hokkaido University, Sapporo, Japan.

Department of Renal and Urologic Surgery, Asahikawa Medical University, Asahikawa, Japan.

出版信息

Low Urin Tract Symptoms. 2023 Nov;15(6):265-270. doi: 10.1111/luts.12503. Epub 2023 Sep 18.

Abstract

OBJECTIVES

Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β -adrenoceptor agonist approved for the treatment of overactive bladder. However, how β -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease.

METHODS

In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity.

RESULTS

Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed.

CONCLUSIONS

The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β -adrenoceptor agonists.

摘要

目的

由多巴胺能神经元丧失引起的帕金森病不仅导致运动功能障碍,还导致下尿路功能障碍。最近有报道称,帕金森病患者同时患有急迫性尿失禁(膀胱过度活动症)和压力性尿失禁,后者是当膀胱压力超过尿道压力时发生的。维贝格隆是一种新型高选择性β-肾上腺素受体激动剂,获批用于治疗膀胱过度活动症。然而,β-肾上腺素受体激动剂如何影响尿道功能仍不清楚。在一项临床报告中,显示帕金森病患者的尿道功能下降。本研究旨在探讨维贝格隆对帕金森病大鼠模型下尿路活动的影响。

方法

在单侧 6-羟多巴胺注射到黑质致密部诱导的帕金森病大鼠模型中,我们研究了维贝格隆对膀胱和尿道活动的影响。

结果

膀胱测压分析显示,与载体注射相比,静脉注射 3mg/kg 维贝格隆显著增加了膀胱收缩间期(p<0.05)并降低了排尿压(p<0.01)。然而,对尿道功能没有显著影响。

结论

本研究结果提供了佐证,表明在帕金森病模型大鼠中,维贝格隆给药可抑制膀胱功能障碍,证实维贝格隆对治疗膀胱过度活动症有效,而不会进一步恶化尿道功能。这些发现可能有助于更好地理解β-肾上腺素受体激动剂的作用机制。

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