PDGF/PDGFR信号对胰岛移植物损伤修复与增殖的影响及其机制研究

How to reduce islet graft loss post-transplant, to maintain long-term survival of a certain amount of islet allograft is currently a hot research. However, lack of early revascularization of islet graft post-transplant, and low capacity of mature islet cell proliferation are closely related with massive loss islet grafts..Platelet-derived growth factor (PDGF) has a strong ability to repair tissue damage and promote angiogenesis effect. The latest research shows that: the decreased expression of platelet-derived growth factor receptor (PDGFR) is a key to loss of the proliferative capacity of mature pancreatic β cell. By upregulating the expression of PDGFR or given exogenous PDGF, can regain the ability to self-replicate islet proliferation, restoration of the islet damage, and significantly improve the ability of regulate blood sugar of islet. Therefore, this study envisaged: whether through supplementary exogenous PDGF or PDGFR gene transfer, to increase the proliferation and repair capacity of islet graft, promote angiogenesis, reconstruction the number and function of islet in transplant recipients. If successful, it is significant for solving many questions that exist in the field of islet transplantation, to reduce the amount of islet transplantation, alleviate shortage of donor islet transplantation, and promote functional islet graft survival and other issues.

如何减少胰岛移植后早期大量丢失，保持一定数量的胰岛移植物长期存活是目前研究的热点，而胰岛移植后早期再血管化不足，以及成熟胰岛细胞增殖能力低下与此密切相关。.血小板衍生生长因子（PDGF）具有较强的组织损伤修复能力和促进血管新生的作用；而最新的研究表明，血小板衍生生长因子受体PDGFR表达降低是成熟胰岛β细胞丧失增殖能力的关键，通过上调PDGFR表达水平或给予外源PDGF，可使胰岛重新获得自我复制增殖的能力，并且显著改善胰岛调节血糖的能力。因此，本课题设想，能否通过给予外源PDGF或者导入PDGFR基因，来增加移植胰岛的增殖与修复能力，促进新生血管形成，重建受体体内的胰岛β细胞总量和功能。若获成功，对于减少胰岛移植的细胞量以缓解胰岛移植供体匮乏，促进移植物有功能存活等问题有重要意义。

如何减少胰岛移植后早期大量丢失，保持一定数量的胰岛移植物长期存活是目前研究的热点，而胰岛移植后缺血再灌注、氧化应激和炎性损伤，以及成熟胰岛细胞增殖能力低下与此密切相关。血小板衍生生长因子（PDGF）具有较强的组织损伤修复能力和促进血管新生的作用；而最新的研究表明，血小板衍生生长因子受体PDGFR表达降低是成熟胰岛β细胞丧失增殖能力的关键，通过上调PDGFR表达水平或给予外源PDGF，可使胰岛重新获得自我复制增殖的能力，并且显著改善胰岛调节血糖的能力。本课题验证了，通过给予外源PDGF或者导入PDGFR基因，促进移植胰岛的增殖与修复能力、和抗凋亡能力，增强胰岛功能，改善局部氧化应激和炎症反应，重建受体体内的胰岛β细胞总量和功能。本项目的研究结果，对于减少胰岛移植的细胞量以缓解胰岛移植供体匮乏，促进移植物有功能存活等问题有重要意义。