Activation of VEGF and ERK1/2 and Improvement of Urethral Function by Adipose-derived Stem Cells in a Rat Stress Urinary Incontinence Model
Activation of VEGF and ERK1/2 and Improvement of Urethral Function by Adipose-derived Stem Cells in a Rat Stress Urinary Incontinence Model
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DOI：
10.1016/j.urology.2012.05.030
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发表时间：
2012-10-01
期刊：
影响因子：
2.1
通讯作者：
Xin, Zhong-Cheng
中科院分区：
文献类型：
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作者：
Li, Guang-Yong;Zhou, Feng;Xin, Zhong-Cheng
目的探讨自体脂肪来源干细胞(ADSCs)对产后压力性尿失禁大鼠模型的改善作用及其可能机制。从卵巢周围脂肪中分离ADSCs，用胸腺嘧啶核苷类似物5-乙炔-2-脱氧尿苷(EDU)标记。20只压力性尿失禁大鼠经尿路注射磷酸盐缓冲液作为阴性对照，20只压力性尿失禁大鼠经尿路注射EDU标记的ADSCc。对照组大鼠20只，行假手术切除卵巢，不扩张球囊，作为阳性对照。4周后行膀胱测压评价排尿功能。结果与球囊损伤去卵巢大鼠相比，ADSC治疗组大鼠漏尿点压力和膀胱容量均显著增加。组织学检查显示，ADSC处理的大鼠的尿路纤维肌肉结构外观正常，尿路周围血管密度增加。免疫印迹显示ADSC治疗组大鼠组织中血管内皮生长因子和P-细胞外信号调节蛋白(ERKs)1/2蛋白的表达高于磷酸盐缓冲生理盐水治疗组大鼠。结论经尿道周围注射ADSCs可促进产后尿失禁大鼠正常的排尿功能和尿路结构。血管内皮生长因子和ERK1/2的激活可能与ADSCs的旁分泌作用有关。泌尿外科80：953.e1-953.e8,2012年。(C)2012年爱思唯尔公司。
OBJECTIVE To investigate the injected autologous adipose-derived stem cells (ADSCs) in improving stress urinary incontinence in a rodent model of parturition-related stress incontinence and the possible mechanism.METHODS The 40 rats were developed stress urinary incontinence models by postpartum balloon dilation of the vagina for 4 hours followed by bilateral ovariectomy. ADSCs were isolated from the peri-ovarian fat and labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU). Twenty stress urinary incontinence rats received peri-urethral injection of phosphate-buffered saline as the negative controls and the other 20 stress urinary incontinence rats received peri-urethral injection of EdU-labeled ADSCc. Twenty control rats underwent sham ovariectomy without balloon dilation and served as positive controls. Four weeks later, voiding function was assessed by cystometry. Urethral histologic examination (Masson trichrome stain, picrosirius red stain, Hart elastin stain, Gordon and Sweet stain, and immunohistochemical stain) and Western blot were performed on urethral tissues.RESULTS Both leak point pressure and bladder capacity were significantly increased in ADSC-treated rats, compared to the balloon-injured ovariectomized rats. Histologic examination revealed normalized appearance of the fibromuscular structure of the urethra as well as increased peri-urethral blood vessel density in ADSC-treated rats. On Western blot, vascular endothelial growth factor and P-extracellular signal-regulated kinases (ERKs)1/2 protein was expressed at a higher rate in tissues from ADSC-treated rats compared to phosphate-buffered saline-treated rats.CONCLUSION Peri-urethral injection of ADSCs is associated with more normal urinary function and urethral structure in rats with parturition-related incontinence. The activation of vascular endothelial growth factor and ERK1/2 may be responsible for the paracrine effects from ADSCs. UROLOGY 80: 953.e1-953.e8, 2012. (C) 2012 Elsevier Inc.