School of Medicine, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan.
Division of Urology, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824005, Taiwan.
Int J Mol Sci. 2024 Oct 16;25(20):11103. doi: 10.3390/ijms252011103.
Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO's impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2/HIF-1α signaling pathway in MetS with or without OHD-induced OAB.
代谢综合征（MetS）包括心血管危险因素，如肥胖、血脂异常、高血压和葡萄糖耐量异常，这些因素会增加膀胱过度活动症（OAB）的风险，其特征为尿急、尿频、急迫性尿失禁和夜尿症。代谢综合征和卵巢激素缺乏（OHD）都与膀胱过度活动有关。一氧化氮（NO）已知具有抗炎和促进愈合的作用，但它对代谢综合征和 OHD 中膀胱过度活动的影响尚不清楚。本研究旨在探讨 NO 对代谢综合征和 OHD 大鼠逼尿肌过度活动的影响。雌性 Sprague-Dawley 大鼠根据饮食和治疗分为七组，涉及 L-精氨酸（NO 前体）和 L-NAME（NOS 抑制剂）。在高脂肪、高糖饮食 12 个月后，进行膀胱测压和排尿行为轨迹分析，以确定逼尿肌过度活动的症状。有或没有 OVX 的代谢综合征伴有或不伴有 OHD 组的膀胱收缩反应更差，而 L-精氨酸改善了膀胱收缩功能。综上所述，有或没有 OHD 的代谢综合征会降低 NO 产生、减少血管生成，并增强氧化应激，导致膀胱过度活动，这是通过 NF-kB 信号通路介导的，而 L-精氨酸通过 NRF2/HIF-1α 信号通路改善了有或没有 OHD 诱导的 OAB 大鼠的逼尿肌过度活动症状，并减轻了氧化损伤。
