双模态分子成像评价活体胰岛移植IBMIR非免疫损伤

Islet transplantation offers a potential treatment for typeⅠdiabetes that could normalize blood glucose levels and circumvent the development of complications commonly associated with this disease. One major problem in the field of intraportal islet transplantation is that large amounts of cells are lost at the time of infusion into the portal vein, resulting in a low level of engraftment of the islets. Immediately blood-mediated inflammatory reaction (IBMIR) is a critical reason for the resulting portal vein thrombosis and graft failure and is a thrombotic/inflammatory reaction occurring when islets come in contact with host blood. The IBMIR is characterized by coagulation and complement activation, leading to platelet consumption, leukocyte infiltration of the islets, and disruption of islet integrity. It would be of great value to improve the effectiveness of islets transplantation and to decrease donor numbers. Current methods to assess IBMIR are hematological indexes including detecting the activation of coagulation, complement and leukocyte infiltration. But these methods are not in real-time and could be easily disturbed. Hence, the current methods for assessing IBMIR all have considerable limitations. To expedite the study of IBMIR during islet transplantation, novel markers for detecting IBMIR are highly needed. Molecular imaging may be the best choice. This study will specially image the IBMIR of islet transplantation by optical molecular imaging technology. Thereby to establish an optical molecular imaging method to qualitatively and quantitatively evaluate the damage of islets during the first period of transplantation and provide the fundamental and theoretical evidences for further developments of animal experiments and clinical applications.

胰岛移植是治疗I型糖尿病的极有前景的方法。但移植初期大量胰岛（约80％）即被破坏或功能受损，主要原因是立即经血液介导的炎症反应(IBMIR)，激活血小板，引起凝血和补体的瀑布式级联反应，导致胰岛损伤和丢失，是一种早期、快速、剧烈、非特异性免疫排斥的炎症反应，抗免疫排斥反应治疗无效。目前研究方法不能实时、灵敏、精准的反映活体IBMIR发生程度，及其对胰岛细胞的损伤情况，需探索新的检测方法，分子影像的发展为其提供了可能。本研究项目拟采用光学探索SCID鼠活体胰岛移植IBMIR的分子成像，同时采用分子探针标记胰岛并采用光学成像方法实时显示体内胰岛的损伤情况，分析光学分子成像结果，建立光学分子成像定性和定量评估移植初期胰岛损伤的检测方法。

胰岛移植是治疗I型糖尿病的极有前景的方法，其最主要的移植途径是经门静脉移植到肝脏内。但移植初期，胰岛与血液接触后会发生剧烈的立即经血液介导的炎症反应(IBMIR)，大量胰岛（约80％）即被破坏或功能受损，导致胰岛损伤和丢失。本项目旨在探讨光学分子影像技术实时监测移植初期的IBMIR及胰岛存活情况。IBMIR的重要特征是凝血系统被激活，胰岛周围血栓形成，血栓可以作为IBMIR发生程度的标志物。本研究团队构建了SCID mice活体肝脏门静脉系统胰岛移植IBMIR动物模型；采用靶向血栓的KGDS光学探针，建立了实时显示血栓形成的分子影像平台；同时采用荧光染料-DID，与胰岛共孵育，标记胰岛移植物，利用光学分子影像技术实时显示胰岛在活体的定位情况。通过对靶向血栓的KGDS分子探针特性的检测，证实其可以靶向结合在新鲜血栓上，从而可以实时提示IBMIR的发生，首次采用光学分子影像的方法，无创、实时地显示IBMIR的发生。利用荧光染料标记胰岛，活体实时显示胰岛在肝脏的定位，从而一定程度上实时监测胰岛的存活情况。本研究团队还尝试合成纳米光学分子探针，探索在胰岛移植IBMIR的应用，结果发表在国际著名期刊《J Nanopart Res》上。. 我们在基金委的资助下，如期完成了该课题的研究内容和研究目标，取得了一些研究成果，发表了标注本项目资助号的论文5篇，其中SCI 收录论文4篇，Medline 收录论文1篇；另有1篇论文被国际移植大会收录并作大会报告。