双分子探针探索TF表达沉默阻断胰岛移植中IBMIR非免疫损伤的实验研究

项目名称： 双分子探针探索TF表达沉默阻断胰岛移植中IBMIR非免疫损伤的实验研究

项目编号： No.81201171

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 马小倩

作者单位： 中南大学

项目金额： 23万元

中文摘要： 胰岛移植是建立内源性胰岛素分泌系统治疗I型糖尿病最有效的方法。立即经血液介导的炎症反应（IBMIR）是影响胰岛移植疗效的第一个关键因素。组织因子TF是激发IBMIR的始动因子，血栓形成是IBMIR的重要特征。前期研究证实，特异性靶向TF的反义RNA在体外IBMIR模型中能初步阻断IBMIR发生。但是在复杂的体内环境中TF沉默能否抑制IBMIR？如何活体实时监测移植过程中IBMIR的发生？这是我们需要进一步解决的问题。本项目拟利用靶向TF的shRNA-GFP作为胰岛细胞TF沉默及示踪的分子探针，结合特异性血栓靶向的小分子荧光探针，利用双分子探针分子影像技术实时无创地监测移植过程中TF沉默胰岛细胞是否阻断IBMIR发生;通过长期监测糖尿病鼠的血糖变化及病理检测移植物存活情况，评估IBMIR的发生程度,判断分子探针的灵敏度。该项目的研究将为我们在胰岛移植中进行IBMIR监测及移植物保护提供新方法

中文关键词： 胰岛；移植；立即经血液介导的炎性反应；组织因子；反义RNA

英文摘要： Islet transplantation is an effective treatment for type I diabetics by reconstituting endogenous insulin secreting tissue. Instant blood mediated inflammatory reaction (IBMIR) is a first key factor affecting the efficacy of islet transplantation. Tissue factor (TF) has been proved as the trigger of IBMIR with thrombosis as its featured characteristic. We have previously shown that IBMIR can be blocked in an in vitro IBMIR model by s TF antisense RNA-mediated silencing of TF expression in islets. In order to determine whether IBMIR can be also blocked in vivo by TF silencing and investigate whether the development of IBMIR during and after islet transplantation can be monitored, we aim to develop a non-invasive and real-time monitoring technology to evaluate in vivo inhibition of IBMIR by TF silencing using a TF silencing and tracing molecular probe, shRNA-GFP to target TF along with a thrombus targeted molecular fluorescent probe to detect IBMIR. This study will provide a new technology to monitor IBMIR in vivo, thereby leading to the development of a clinically applicable treatment to protect islet graft against IBMIR.

英文关键词： islet；transplantation；IBMIR；Tissue factor；antisense RNA