胰岛移植是治愈糖尿病和缓解糖尿病并发症最有前景的治疗手段和方法，但如何避免胰岛移植物在受体内的早期缺氧死亡仍是这一领域亟需解决的难题。我们前期研究发现，缺氧诱导的胰岛细胞死亡能被程序性坏死抑制剂Nec-1显著抑制。缺氧导致了胰岛细胞内NF-KB信号通路激活，促进了TNFα等炎性因子的表达上调。本项目将以缺氧诱导的程序性坏死和炎性反应为切入点，利用分子影像学探针对移植物体内缺氧环境进行标记，通过纳米材料Ferritin对Nec-1有效包裹并实现其在缺氧局部的智能化释放，同时结合TNFR拮抗剂联合干预缺氧导致的胰岛细胞死亡。本项目将建立胰岛移植中“缺氧-TNFα-程序性坏死”的新联系，为促进胰岛移植过程中对胰岛缺氧的检测和保护，防止胰岛细胞早期死亡这一重要问题提供前期的实验依据。

Islet transplantation is the most promising therapy strategy in curing diabetes. Yet how to avoid the early death of islet grafts induced by hypoxia is still a problem which is urgently needed to be solved. In our previously study, we found that islet death induced by hypoxia could be significantly inhibited by necroptosis inhibitor Nec-1. Hypoxia can activate NF-KB signal pathway in islet cells and can up-regulate the expression of some pro-inflammatory cytokines such as TNFα. This study will take hypoxia induced necroposis and inflammatory response as a breakthrough point and label the hypoxia environment in grafts using molecular imaging probe. Then we will utilize nanomaterial Ferritin for Nec-1 package to realize the Nec-1 intelligent release in hypoxia sites. In the mean time, we will intervene the hypoxia induced islet cell death by TNFR antagonist combination drug therapy. This study will establish the new connection of “hypoxia-TNFα-necroptosis” in islet transplantation. Thus, provide a fundamental experiment basis for this important issue, that is, to detect and protect the islet hypoxia during islet transplantation and prevent islet grafts from early death.