特异性靶向纳米载体联合AQP1-siRNA对子宫内膜异位症的作用及其机制研究

项目名称： 特异性靶向纳米载体联合AQP1-siRNA对子宫内膜异位症的作用及其机制研究

项目编号： No.81200428

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 赵梦丹

作者单位： 浙江大学

项目金额： 24万元

中文摘要： 子宫内膜异位症的病因及发病机制不明，导致临床治疗对策缺乏。生物治疗是近几年的研究热点。采用特异性小分子干扰RNA，可沉默并阻断内异细胞AQP1的表达及相关信号途径，从而起到治疗内异症的效果，但siRNA对内异细胞的导入是关键。本项目以基因载体的高效、低毒为目标，采用具有细胞器靶向功能的非病毒载体，研究其介导siRNA给药系统的细胞内转运和亚细胞器靶向，减少巨噬细胞和正常细胞的摄取，延长体内循环时间，提高内异组织分布；考察卵巢和子宫以及病灶AQP1的表达水平，病灶体积、重量、VEGF表达水平、血管密度及细胞凋亡指数，血液性激素水平变化，以及卵巢和子宫的组织形态改变并分析AQP1-siRNA在治疗内异症过程中的信号通路；探索新型靶向纳米载体介导AQP1-siRNA治疗内异症的有效性与安全性，并研究其作用机制，为最终用于临床治疗内异症，提供新理论、新方法和新途径。

中文关键词： 子宫内膜异位症；AQP1-siRNA；靶向；基因治疗；动物模型

英文摘要： The etiology and pathogenesis of endometriosis is still unclear which result in the lack of clinical treatment countermeasures. Biological treatment is a research hotspot in recent years. The expression of AQP1 in endometriosis cells and related signaling pathways can be silent and blocked by using the specific small interfering RNA, which play the effect of treatment of endometriosis. But the key is how to put the siRNA into endometriosis cells. In this project, we design the organelle-targeted non-viral vectors with the high efficiency and low toxicity as the goal. The drug delivery system of the AQP1-siRNA mediated with the nanoparticle was studied for intracellular transport and subcellular targeting, which reduced the cellular uptake of macrophage and normal cells, extended circulation time in vivo, and improved the endometriosis tissue distribution. The expression level of AQP1 in ovaries, uterus and lesion was examined. The lesion size, weight, VEGF expression, vascular density and apoptosis index, blood hormone levels, and ovarian and changes in uterine morphology were studied and AQP1-siRNA in the treatment of endometriosis with the process of signaling pathways was analysised. Then study the mechanism of AQP1-siRNA gene therapy and explore the feasibility of the siRNA gene therapy on endometriosis. And

英文关键词： Endometriosis；AQP1-siRNA；targeting；gene therapy；animal models