Sun Shuwen, Zhang Jingcheng, Ainiwaer Ailiyaer, Liu Yuchao, Shen Danjing, Jiang Yufeng, Chen Hanyang, Bohetiyaer Ayinuer, Wu Tong, Gao Yuchen, Li Wei, Xu Yunfei, Xu Tianyuan, Yan Yang
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China.
Transl Androl Urol. 2025 Aug 30;14(8):2254-2268. doi: 10.21037/tau-2025-234. Epub 2025 Aug 26.
Neurogenic bladder (NB) refers to urinary storage and voiding dysfunction resulting from neurological disorders. Animal models of NB are commonly used in preclinical studies, but the distinct characteristics of various modeling techniques are infrequently compared. This study aimed to evaluate and compare the functional and pathological outcomes of different NB rat models.
Three rat NB models were induced by spinal cord injury (SCI), bladder outlet obstruction (BOO), and diabetes. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels, along with urine flow dynamics, were assessed at weeks 1, 2, 4, and 8. At the 10-week endpoint, animals were euthanized, and bladder weights were recorded for each specimen. Pathological analysis and western blotting were conducted to evaluate bladder muscle fibrosis.
All three rat NB models were successfully established. At week 8, the average maximum/minimum bladder pressures for the SCI, BOO, and diabetic NB rats were 34.0/27.8, 40.4/30.2, and 32.1/28.8 mmHO, respectively, while bladder capacity and residual volumes were 4.32/4.245, 5.35/5.084, and 4.20/4.048 mL, respectively. The average Scr levels were 52.2, 54.6, and 37.7 mmol/L, and BUN levels were 15.4, 13.8, and 13.9 mmol/L for the three groups. Compared to the control, bladder weights and volumes were significantly increased in the NB groups. Histopathological examination revealed marked thickening and disorganization of the muscle bundles in NB bladders, along with notable inflammatory cell infiltration within the epithelial layer. Immunohistochemical and western blot analyses showed increased fibronectin expression in the NB model bladders.
The three NB rat models effectively replicated clinical and pathological features, including reduced bladder compliance, renal dysfunction, and bladder fibrosis. Among these models, SCI offers the fastest method for inducing NB. Renal function impairment was more pronounced in the SCI- and BOO-induced NB models, with BOO resulting in the most significant pathological changes in the bladder.
神经源性膀胱(NB)是指由神经系统疾病导致的膀胱储尿和排尿功能障碍。NB动物模型常用于临床前研究,但各种建模技术的独特特征鲜少被比较。本研究旨在评估和比较不同NB大鼠模型的功能和病理结果。
通过脊髓损伤(SCI)、膀胱出口梗阻(BOO)和糖尿病诱导建立三种大鼠NB模型。在第1、2、4和8周评估血尿素氮(BUN)和血清肌酐(Scr)水平以及尿流动力学。在第10周的终点,对动物实施安乐死,并记录每个标本的膀胱重量。进行病理分析和蛋白质印迹法以评估膀胱肌肉纤维化。
所有三种大鼠NB模型均成功建立。在第8周时,SCI、BOO和糖尿病NB大鼠的平均最大/最小膀胱压力分别为34.0/27.8、40.4/30.2和32.1/28.8 mmHO,而膀胱容量和残余尿量分别为4.32/4.245、5.35/5.084和4.20/4.048 mL。三组的平均Scr水平分别为52.2、54.6和37.7 mmol/L,BUN水平分别为15.4、13.8和13.9 mmol/L。与对照组相比,NB组的膀胱重量和体积显著增加。组织病理学检查显示NB膀胱中肌束明显增厚和紊乱,上皮层内有明显的炎性细胞浸润。免疫组织化学和蛋白质印迹分析显示NB模型膀胱中纤连蛋白表达增加。
三种NB大鼠模型有效地复制了临床和病理特征,包括膀胱顺应性降低、肾功能障碍和膀胱纤维化。在这些模型中,SCI提供了诱导NB最快的方法。SCI和BOO诱导的NB模型中肾功能损害更为明显,BOO导致膀胱中最显著的病理变化。