胰岛移植是根治糖尿病的重要方法，但胰岛移植早期的血管新生不良是其应用于临床的主要障碍之一。我们前期研究发现骨髓间充质干细胞（BMSCs）与胰岛联合移植可改善胰岛血管新生情况，胰岛素基因增强子结合蛋白-1（ISL1）作为激活血管内皮生长因子（VEGF）转录的重要因子，在血管新生良好的胰岛中表达水平升高。我们利用亲和纯化联合质谱及免疫共沉淀发现p65能与ISL1相互作用，且p65激活与VEGF的表达水平显著相关。据此我们提出科学假说：BMSCs诱导胰岛中ISL1高表达，与p65相互作用增强VEGF转录，在胰岛血管新生中发挥重要作用。本项目拟利用酵母双杂交检测、染色质免疫沉淀等分子生物学技术解析ISL1与p65相互作用的机制，并通过构建糖尿病大鼠胰岛移植模型，明确ISL1与p65相互作用可促进胰岛血管新生、提高胰岛移植存活率，为胰岛移植改善缺血缺氧的微环境奠定理论基础并探索出新的防治策略和途径。

Islet transplantation is an important method to cure diabetes mellitus, but poor angiogenesis in the early stage of islet transplantation is one of the major obstacles to its clinical application. Our previous studies have found that bone marrow mesenchymal stem cells (BMSCs) combined with islet transplantation can improve islet angiogenesis. Insulin gene enhancer binding protein-1 (ISL1), as an important transcription factor in vascular endothelial growth factor (VEGF) activation, is highly expressed in islets with ideal angiogenesis status. p65 can interact with ISL1 by affinity purification combined with mass spectrometry and immunoprecipitation, and the activation of p65 is positively correlated with the expression of vascular endothelial growth factor. Accordingly, we propose the following scientific hypothesis: BMSCs can induce ISL1 overexpression in islets, which in turn enhance the transcription of vascular endothelial growth factor via interaction with p65, therefore play an important role in islet angiogenesis. This project aims to establish a diabetic rat islet transplantation model, analyze the interaction and mechanism between ISL1 and p65 with yeast two-hybrid assay, chromatin immunoprecipitation and other molecular techniques. And to investigate whether the interaction between ISL1 and p65 can promote islet angiogenesis, leading to improved the survival rate of islet transplantation. Our hope is this project can lay a theoretical foundation for developing novel methods to improve the ischemic and hypoxic microenvironment of islet transplantation, exploring new strategies in prevention and treatment.