人脐带间充质干细胞移植治疗大鼠压力性尿失禁的研究

摘要

Objective To investigate the feasibility and effectiveness of human umbilical cord mesenchymal stem cells (HUCMSC) transplantation in the treatment of female stress urinary incontinence (SUI) in rats.Methods The 14 female SD rats of SUI model were established by vaginal balloon dilation after birth and maintain this status for four hours bilateral ovariectomy were performed after two weeks and were routinely reared for two months,then 12 SUI rat model were made.Two months later,transfected with plasmid pEGFP-N1 of HUCMSC were injected into the region surrounding the urinary tract matched with saline injection as control group.To get genitourinary tissue after testing urodynamic indicators,and observe the pathological changes of the bladder,urethra and the surrounding tissue; fluorescent cell of the experimental groups specimens were observed by fluorescence microscope.Results The leak point pressure (LPP) was (23.8 ±4.2) mm Hg(1 mm Hg =0.133 kPa) of the SUI rats.Transplanting mesenchymal stem cells of SUI rats,the positive rate of sneeze test was 1/6 in SUI group and 5/6 in control group,which reached statistical significance (P ＜0.05) ; LPP was (30.6 ±2.8) mm Hg in SUI group and (21.4 ±7.0) mm Hg in control group,which reached statistical significance (P ＜ 0.05).In SUI rate model,connective tissue content were increased in urethra and the surrounding tissue and more fluorescent cell were observed.Conclusions A rat model of female SUI was established successfully through postpartum vaginal balloon dilation and bilateral ovariectomy.MSC can be survived and proliferated in the urethral and the surrounding tissue of injured rats,and improve the urodynamic indicators and the positive rate of sneeze test.Morphology shows renovation of the support structures around the urethra.%目的 探讨人脐带间充质干细胞(HUCMSC)移植治疗雌鼠压力性尿失禁(SUI)的可行性和有效性.方法 14只SD大鼠分娩后立即采用气囊压迫大鼠阴道壁4h模拟产伤,2周后行双侧卵巢切除,常规饲养2个月后建成12只SD大鼠SUI模型.建模2个月后,将转染pEGFP-N1质粒的HUCMSC注射于6只SUI大鼠尿道周围(移植治疗组),另6只相同部位注射等量生理盐水(实验对照组),比较两组尿动力学指标后,获取泌尿生殖道组织,观察尿道及其周围组织和膀胱的形态学变化；荧光显微镜观察SUI模型大鼠泌尿生殖道组织标本荧光细胞的分布.结果 成功建模的12只大鼠漏尿点压力值为(23.8±4.2)mm Hg(1 mm Hg=0.133 kPa).移植治疗组喷嚏试验阳性率为1/6,实验对照组为5/6,两组比较,差异有统计学意义(P＜0.05).移植治疗组漏尿点压力值为(30.6±2.8) mm Hg,实验对照组为(21.4±7.0) mmHg,两组比较,差异有统计学意义(P＜0.05).HUCMSC移植治疗后大鼠尿道壁肌层增厚,肌层和筋膜间结缔组织紧密,尿道及周围组织切片可见到荧光细胞分布.结论 采用气囊压迫分娩大鼠阴道壁模拟产伤并行双侧卵巢切除能成功获得稳定的SUI动物模型.HUCMSC可以在损伤的大鼠尿道周围组织中存活、增殖,改善尿流动力学指标和喷嚏试验的阳性率；形态学上观察可修复尿道周围的支持组织.