新型组织工程填充剂治疗尿道内括约肌功能障碍型压力性尿失禁的实验性研究

发布时间：2018-07-27 14:30

【摘要】：压力性尿失禁(Stress Urinary Incontinence, SUI)是妇女常见疾患,指患者腹压突然增加(咳嗽、大哭、喷嚏、体举重物)时,尿液不自主地由尿道口流出。国内发病率为22.9%-35.8%,给患者和社会带来沉重的心理、卫生和经济负担。尿道括约肌细胞凋亡失衡引起括约肌收缩功能减退是导致中老年人群中尿失禁发病率呈上升趋势的主要原因,导致了尿道内括约肌功能障碍(Intrinsic Sphincter Deficiency, ISD)型SUI。针对ISD的治疗方法主要有尿道周围或经尿道注射填充剂如：胶原、聚四氟乙烯等,近期疗效理想,但其远期效果不佳,并常常合并如血肿、移植物转移和移植物暴露等并发症。运用组织工程技术构建尿道组织工程填充剂为ISD的理想治疗提供了新思路,并具备安全、高效、持久、不发生迁移以及低免疫源性的特性,更进一步,其具有促进局部肌肉再生和神经再生,进而恢复自主尿道控制力的潜能。种子细胞和支架材料为组织工程组织构建的两大核心要素。因脂肪源性干细胞(ADSCs)具有取材方便、来源广泛、储备丰富、易于体外培养、可稳定扩增且具有多向分化潜能,被认为是理想的组织再生的种子细胞’来源。蚕丝是天然生物材料,以其良好的生物相容性、优越的力学性能、低免疫应答反应、可降解性、可塑性和缓释性,具备了在组织工程与再生医学领域应用的良好前景。在我们的研究中,利用ADSCs复合丝素蛋白微球构建尿道组织工程填充剂用于ISD大鼠的治疗,一方面通过丝素蛋白微球的注射对膀胱颈提供支持填充,产生即时的治疗效果；另一方面又通过复合于丝素蛋白微球上的ADSCs的移植,继发的细胞分化与增殖,促进局部肌肉和神经再生,改善尿道括约肌结构和功能缺陷,从而提高尿道括约肌的控尿能力,达到持久的治疗效果。该新型的组织工程填充剂在大鼠ISD模型上取得了初步疗效,积累了临床前研究资料,为临床上ISD的治疗提供新的策略和理论依据,展示了广阔的临床应用前景。
[Abstract]:Stress urinary incontinence (Stress Urinary Incontinence, SUI) is a common disorder in women. It occurs when abdominal pressure increases (cough, crying, sneezing, weight lifting), and urine flows involuntarily from the urethra. The incidence rate in China is 22.9- 35.8B, which brings heavy psychological, health and economic burden to patients and society. The decrease of sphincter contractile function caused by the imbalance of apoptosis of sphincter cells in urethra is the main cause of increasing incidence of urinary incontinence in middle-aged and elderly population, which leads to (Intrinsic Sphincter Deficiency, ISD) type sui of urethral sphincter dysfunction. The main treatment methods for ISD include periurethral or transurethral injection of fillers such as collagen, PTFE, etc. The short-term curative effect is ideal, but its long-term effect is not good, and often complicated with complications such as hematoma, graft metastasis and graft exposure. Using tissue engineering technology to construct urethral tissue engineering fillers provides a new idea for the ideal treatment of ISD, and has the characteristics of safety, efficiency, persistence, non-migration and low immunogenicity. It has the potential to promote local muscle regeneration and nerve regeneration, and then restore the autonomic urethral control. Seed cells and scaffolds are two core elements of tissue engineering. Adipogenic stem cell (ADSCs) is an ideal source of seed cells for tissue regeneration because of its advantages of convenient selection, wide source, abundant reserve, easy to be cultured in vitro, stable amplification and multidirectional differentiation potential. Silk is a natural biomaterial, with its good biocompatibility, superior mechanical properties, low immune response, degradability, plasticity and slow release, it has a good prospect in the field of tissue engineering and regenerative medicine. In our study, urethral tissue engineering fillers were constructed with ADSCs composite fibroin microspheres for the treatment of ISD rats. On the one hand, the bladder neck was supported and filled with fibroin microspheres, which produced immediate therapeutic effect. On the other hand, the secondary cell differentiation and proliferation through the transplantation of ADSCs combined with fibroin microspheres, promote local muscle and nerve regeneration, improve the defect of the structure and function of the urethral sphincter, so as to improve the urinary control ability of the urethral sphincter. Achieve a lasting therapeutic effect. The new tissue engineering filler has obtained the initial curative effect on the rat ISD model, accumulated the data of preclinical research, provided the new strategy and theory basis for the clinical treatment of ISD, and showed the broad clinical application prospect.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.59

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