ATF诱导Th1/Th2漂移构建血管化人工胰岛的研究

项目名称： ATF诱导Th1/Th2漂移构建血管化人工胰岛的研究

项目编号： No.31470046

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 侯春丽

作者单位： 中国人民解放军第三军医大学

项目金额： 30万元

中文摘要： 糖尿病已成为威胁人类健康的一大杀手。胰岛移植被公认为是糖尿病尤其是I型糖尿病最具前景的治疗方法，但其远期临床效果并不理想，绝大多数接受胰岛移植的患者在几年内又恢复了胰岛素依赖。本项目针对HO-1这一重要的抗氧化酶，不但可以抑制高糖、缺氧等诱导的内皮细胞损伤，而且在降低移植物免疫排斥反应中具有重要作用，基于课题组前期获得的一种新型人工转录因子（ATF）能特异促进细胞内源性HO-1持续高表达，以及EPC促进血管新生的作用，拟通过将HO-1高表达的EPC和胰岛细胞共移植，揭示：1.HO-1在EPC促胰岛内血管快速重建、提高血管密度中的作用及机制；2.HO-1在诱导Th1/Th2漂移，抑制免疫排斥反应中的作用及机制。3.HO-1 高表达的EPC与胰岛复合水凝胶在治疗糖尿病中的作用及机制。课题的完成将为胰岛移植彻底治疗糖尿病提供重要的临床前实验结果。

中文关键词： 糖尿病；胰岛共移植；骨髓间充质干细胞；血红素加氧酶-1；水凝胶

英文摘要： Diabetes has become a major killer to human health.Islet transplantation is recognized as the most promising treatment method for diabetes especially type I diabetes. However, the long-term clinical effect is not ideal, the majority of patients undergoing islet transplantation restore the insulin dependent in few years after islet transplantation. The research will provide important preclinical experimental results for the treatment of diabetes through islet transplantation.. Heme oxygenase-1( HO-1) is an important antioxidant, it can not only protect endothelial cells against high glucose and hypoxia, but also inhibit immune rejection. Our team have obtained a new artificial transcription factors (ATF), it can specifically promote the continuous expression of endogenous HO-1, EPC play an important role in promoting angiogenesis, we intend to make clear the following questions through diabetic mouse model and 3D thermosensitive hydrogel. 1.The effect and mechanism of ATF on promoting HO-1 expression in EPC and islet cells. 2.Whether ATF can protect EPC against high glucose, hypoxia injury and what is the mechanism. 3.Whether ATF can induce Th1/Th2 drift in islet and inhibit immune rejection. 4.Whether EPC and islet modified by ATF and complex with 3D thermo- sensitive hydrogel can contribute to the treatment fo

英文关键词： diiabetes；islet co-transplantation；MSC；HO-1；hydrogel