Mesh : Humans Rats Female Animals Urinary Bladder, Overactive / genetics Urinary Bladder Neck Obstruction / metabolism Carbachol / pharmacology Urinary Bladder / pathology Cholinergic Agents / metabolism

来  源:   DOI:10.1038/s41598-023-45014-5   PDF(Pubmed)

Abstract:
Overactive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin-eosin (H&E) and Masson\'s trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression.
摘要:
膀胱过度活动症(OAB)是常见的,长期症状复杂,在全球女性中患病率高。OAB造成了社会负担,迫切需要有效的治疗。然而,OAB的发病机制尚未阐明。模型大鼠行膀胱出口梗阻手术。在第二,3rd,手术后第4周,采用代谢笼检测假手术组和模型组大鼠12h尿量。尿动力学参数膀胱漏点压力(BPLL),最大排尿压力(MVP),剩余体积(RV),最大膀胱容量(MBC),膀胱顺应性(BC),无效效率(VE),还检测到非排泄收缩(NVC)。此外,在上述时间点检查了孤立的逼尿肌对电刺激和卡巴胆碱刺激的收缩反应。手术后第4周,两组膀胱均进行苏木精-伊红(H&E)和Masson三色染色。进行实时qPCR和Western印迹以定量胆碱乙酰转移酶(ChAT)和溶质载体家族17成员9(SLC17A9)的表达。在第4周,与假手术组相比,PBOO组12h尿量明显增加。BLPP,MVP,VE,MBC,NVCs显著增加,4周PBOO组VE明显降低。在4周的PBOO组中,孤立的逼尿肌对电刺激和卡巴胆碱刺激的收缩反应显着增加。在为期4周的PBOO组中,膀胱壁和膀胱平滑肌层壁内膀胱肌肉与胶原的比率明显高于假手术组。ChAT和SLC17A9mRNA和蛋白在OAB模型大鼠中的表达显著增加。PBOO后4周,成功建立了OAB模型。在OAB模型的膀胱中ChAT和SLC17A9的基因和蛋白表达水平升高,提示OAB可能与兴奋性嘌呤和胆碱能表达增加有关。
公众号