轉(zhuǎn)化生長因子復合脂肪源性干細胞調(diào)控改造盆腔器官脫垂病理微環(huán)境的機制和效應研究
發(fā)布時間：2019-03-30 17:11
【摘要】：盆腔器官脫垂(POP)是困擾中老年婦女的常見病,目前尚缺乏能夠針對病因的治療方法。現(xiàn)有結(jié)果顯示POP病人的陰道組織中彈性纖維排列紊亂、含量減少,證實了盆底支持結(jié)構(gòu)破壞可能成為POP的病理因素。我們根據(jù)POP臨床改變構(gòu)建并比較了三種動物模型的合理性,結(jié)果證實LOXL1(該基因?qū)椥缘鞍椎暮铣珊徒宦?lián)起重要作用)敲除老鼠不僅會出現(xiàn)穩(wěn)定的POP表型,且盆底彈性纖維及膠原合成和排列也出現(xiàn)紊亂,因此認為Loxl1基因敲除老鼠可作為理想的POP動物模型。在找到合理的POP動物模型后,我們制作了 一種絲素微球,復合經(jīng)TGFβ-1預處理的脂肪來源干細胞來制備可注射絲素-細胞材料,結(jié)果顯示種植在絲素微球中的ADSCs細胞活性良好,且其LOX家族成員以及彈性蛋白的基因表達量上調(diào)。最后將復合ADSC的絲素微球?qū)δＰ托∈筮M行盆底注射,期望增加局部細胞外基質(zhì)的合成和交聯(lián),逆轉(zhuǎn)模型小鼠脫垂表型。本研究期望通過調(diào)控干細胞的表達來調(diào)控彈性蛋白的合成,并復合組織工程技術(shù)手段,為POP的臨床治療提供新思路。
[Abstract]:Pelvic organ prolapse (POP) is a common disease in middle-aged and elderly women. The results showed that the elastic fibers in vaginal tissue of patients with POP were disordered and the content of elastic fibers decreased, which confirmed that the destruction of pelvic floor support structure might be the pathological factor of POP. We constructed and compared the rationality of the three animal models according to the clinical changes of POP. The results showed that LOXL1 (the gene plays an important role in the synthesis and cross-linking of elastin) knockout mice not only showed stable POP phenotypes. Moreover, the synthesis and arrangement of elastic fibers and collagen in pelvic floor were disordered, so it was suggested that Loxl1 knockout mice could be used as an ideal animal model for POP. After finding a reasonable animal model of POP, we made a silk fibroin microspheres combined with adipose-derived stem cells pretreated with TGF 尾-1 to prepare injectable fibroin-cell materials. The results showed that ADSCs cells implanted in silk fibroin microspheres showed good activity, and the expression of LOX family members and elastin genes were up-regulated. Finally, the fibroin microspheres combined with ADSC were injected into the pelvic floor of the model mice in order to increase the synthesis and cross-linking of the local extracellular matrix and reverse the model mice drooping phenotype. The aim of this study is to regulate the synthesis of elastin by regulating the expression of stem cells and to combine tissue engineering techniques to provide a new idea for the clinical treatment of POP.
【學位授予單位】：浙江大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R711.2
本文編號：2450306
[Abstract]:Pelvic organ prolapse (POP) is a common disease in middle-aged and elderly women. The results showed that the elastic fibers in vaginal tissue of patients with POP were disordered and the content of elastic fibers decreased, which confirmed that the destruction of pelvic floor support structure might be the pathological factor of POP. We constructed and compared the rationality of the three animal models according to the clinical changes of POP. The results showed that LOXL1 (the gene plays an important role in the synthesis and cross-linking of elastin) knockout mice not only showed stable POP phenotypes. Moreover, the synthesis and arrangement of elastic fibers and collagen in pelvic floor were disordered, so it was suggested that Loxl1 knockout mice could be used as an ideal animal model for POP. After finding a reasonable animal model of POP, we made a silk fibroin microspheres combined with adipose-derived stem cells pretreated with TGF 尾-1 to prepare injectable fibroin-cell materials. The results showed that ADSCs cells implanted in silk fibroin microspheres showed good activity, and the expression of LOX family members and elastin genes were up-regulated. Finally, the fibroin microspheres combined with ADSC were injected into the pelvic floor of the model mice in order to increase the synthesis and cross-linking of the local extracellular matrix and reverse the model mice drooping phenotype. The aim of this study is to regulate the synthesis of elastin by regulating the expression of stem cells and to combine tissue engineering techniques to provide a new idea for the clinical treatment of POP.
【學位授予單位】：浙江大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R711.2
【參考文獻】
相關(guān)期刊論文 前3條
1 Stuart J Emmerson;Caroline E Gargett;;Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse[J];World Journal of Stem Cells;2016年05期
2 Wen ZONG;Yan JIANG;Jing ZHAO;Jian ZHANG;Jian-gang GAO;;雌激素對賴氨酰氧化酶(LOX)家族基因表達的影響（英文）[J];Journal of Zhejiang University-Science B(Biomedicine & Biotechnology);2015年10期
3 Yang Zhou;Ouyang Ling;Li Bo;;Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction[J];Journal of Biomedical Research;2013年01期
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