新型組織工程填充劑治療尿道內(nèi)括約肌功能障礙型壓力性尿失禁的實(shí)驗(yàn)性研究
發(fā)布時(shí)間：2018-07-27 14:30
【摘要】：壓力性尿失禁(Stress Urinary Incontinence, SUI)是婦女常見(jiàn)疾患,指患者腹壓突然增加(咳嗽、大哭、噴嚏、體舉重物)時(shí),尿液不自主地由尿道口流出。國(guó)內(nèi)發(fā)病率為22.9%-35.8%,給患者和社會(huì)帶來(lái)沉重的心理、衛(wèi)生和經(jīng)濟(jì)負(fù)擔(dān)。尿道括約肌細(xì)胞凋亡失衡引起括約肌收縮功能減退是導(dǎo)致中老年人群中尿失禁發(fā)病率呈上升趨勢(shì)的主要原因,導(dǎo)致了尿道內(nèi)括約肌功能障礙(Intrinsic Sphincter Deficiency, ISD)型SUI。針對(duì)ISD的治療方法主要有尿道周圍或經(jīng)尿道注射填充劑如：膠原、聚四氟乙烯等,近期療效理想,但其遠(yuǎn)期效果不佳,并常常合并如血腫、移植物轉(zhuǎn)移和移植物暴露等并發(fā)癥。運(yùn)用組織工程技術(shù)構(gòu)建尿道組織工程填充劑為ISD的理想治療提供了新思路,并具備安全、高效、持久、不發(fā)生遷移以及低免疫源性的特性,更進(jìn)一步,其具有促進(jìn)局部肌肉再生和神經(jīng)再生,進(jìn)而恢復(fù)自主尿道控制力的潛能。種子細(xì)胞和支架材料為組織工程組織構(gòu)建的兩大核心要素。因脂肪源性干細(xì)胞(ADSCs)具有取材方便、來(lái)源廣泛、儲(chǔ)備豐富、易于體外培養(yǎng)、可穩(wěn)定擴(kuò)增且具有多向分化潛能,被認(rèn)為是理想的組織再生的種子細(xì)胞’來(lái)源。蠶絲是天然生物材料,以其良好的生物相容性、優(yōu)越的力學(xué)性能、低免疫應(yīng)答反應(yīng)、可降解性、可塑性和緩釋性,具備了在組織工程與再生醫(yī)學(xué)領(lǐng)域應(yīng)用的良好前景。在我們的研究中,利用ADSCs復(fù)合絲素蛋白微球構(gòu)建尿道組織工程填充劑用于ISD大鼠的治療,一方面通過(guò)絲素蛋白微球的注射對(duì)膀胱頸提供支持填充,產(chǎn)生即時(shí)的治療效果；另一方面又通過(guò)復(fù)合于絲素蛋白微球上的ADSCs的移植,繼發(fā)的細(xì)胞分化與增殖,促進(jìn)局部肌肉和神經(jīng)再生,改善尿道括約肌結(jié)構(gòu)和功能缺陷,從而提高尿道括約肌的控尿能力,達(dá)到持久的治療效果。該新型的組織工程填充劑在大鼠ISD模型上取得了初步療效,積累了臨床前研究資料,為臨床上ISD的治療提供新的策略和理論依據(jù),展示了廣闊的臨床應(yīng)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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R711.59
本文編號(hào)：2148123
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R711.59
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，本文編號(hào)：2148123
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