miR-155-5p修饰的脂肪干细胞与丝裂霉素C缓释支架材料构建组织工程化尿道在尿路重建中的实验研究

长段复杂性尿道狭窄的重建与预防再狭窄是泌尿外科亟待解决的难题之一，目前临床上制约尿道狭窄治疗效果和导致再狭窄的主要因素为炎性反应所致的成纤维细胞过度增殖。研究提示脂肪干细胞(ASCs)可以抑制新生尿道的炎性反应，但其具体机制并不明确。前期实验提示炎性刺激ASCs后，miR-155-5p表达水平显著上调。本研究通过对ASCs进行慢病毒转染，从而下调ASCs的miR-155-5p的表达水平，并明确miR-155-5p修饰的ASCs对炎性反应的调控作用，探寻相应机制。同时构建并优化缓释丝裂霉素C（MMC）的氧化细菌纤维素，探寻临床应用价值和对纤维瘢痕的抑制作用。之后联合miR-155-5p修饰的ASCs和缓释MMC的支架材料构建组织工程化尿道，在犬尿道缺损模型中评估新生尿道的炎性细胞浸润、纤维增生、支架吸收降解、尿路上皮的爬行及血管化等情况，用以探索更为合理有效的组织工程化尿道方案

Reconstruction and prevention of restenosis of long complex urethral stricture is one of the urgent problems to be solved in urology. At present, the main clinical factor restricting the therapeutic effect of urethral stricture and causing restenosis is the excessive proliferation of fibroblasts caused by inflammatory reactions. Previous studies suggest that adipose-derived stem cells (ASCs) can inhibit the inflammatory response of neonatal urethra, but the specific mechanism is not clear. Previous experiments showed that miR-155-5p expression level was significantly up-regulated after inflammatory stimulation of ASCs. The research down-regulated the expression level of miR-155-5p of ASCs by lentiviral transfection of ASCs, and clarified the regulatory effect of miR-155-5p-modified ASCs on the inflammatory response, and explored the corresponding mechanism. At the same time, the oxidized bacterial cellulose of sustained-release mitomycin c (MMC) was constructed and optimized to explore its clinical application value and its inhibitory effect on fibrous scars. Then, a tissue-engineered urethra combined with miR-155-5p modified adipose-derived stem cells and scaffold material of sustained-release MMC was constructed. In the canine urethral defect model, the inflammatory cell infiltration, fibroproliferation, stent absorption and degradation, vascularization and crawling of urothelial cells of the new urethra were evaluated to explore more reasonable and effective tissue-engineered urethral schemes.