溶血磷脂酸促进内皮祖细胞移植治疗急性肺损伤实验研究

项目名称： 溶血磷脂酸促进内皮祖细胞移植治疗急性肺损伤实验研究

项目编号： No.81460021

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨敬平

作者单位： 内蒙古医科大学

项目金额： 50万元

中文摘要： 肺泡上皮细胞及毛细血管内皮细胞损伤是急性肺损伤（ALI）发病的关键因子，研究发现通过移植内皮祖细胞（EPCs）可修复血管内皮细胞，并能有效治疗ALI。但是，EPCs 增殖能力有限，体外培养中自发分化和凋亡并在移植后大量死亡，限制了治疗效果。溶血磷脂酸（LPA）是活性磷脂，通过膜上的G蛋白偶联受体调控多种细胞生命活动。目前发现，LPA对骨髓分离的造血祖细胞（CD34+）在保持髓样细胞系中起重要作用。前期研究中我们也发现，LPA通过不依赖Gi蛋白的信号途径抑制间充质干细胞的凋亡。因此，我们在该课题中拟复制大鼠ALI模型，从细胞-组织-动物模型三个层次上研究LPA对EPCs存活、迁移活性及EPCs移植效果的影响，并阐明其详细的信号转导机制。LPA作为无免疫原性的生理活性脂质，在抗凋亡并不引起分化等EPCs治疗ALI的关键环节中显示出广泛的应用前景。探索和阐明该应用前景是本课题的目标。

中文关键词： 溶血磷脂酸；内皮祖细胞；急性肺损伤；干细胞移植；信号通路

英文摘要： The injury of alveolar epithelial cell and capillary endothelial cell are key points of acute lung injury(ALI). Those injured cells could be restored after the transplantation of endothelial progenitor cells(EPCs). This maybe be used in treatment of ALI.However, the proliferation ability of EPCs is very limited. The spontaneous differentiation and apoptosis in cell culture, and large death number after transplantation limited the therapeutic effect of EPCs. Lysophosphatidic acid (LPA) is an active phospholipids, it regulates a variety of cellular activities through G protein coupled receptors on cell membrane. A recent study demonstrated LPA may play an important role in maintaining the myeloid cell lines of hematopoietic progenitor cells (CD34 +) which isolated from bone marrow. Our previous study also showed that LPA could inhibit apoptosis of mesenchymal stem cells through Gi protein independent signaling.In this application, we are intending to study the functions of LPA on EPCs survival rate, migration ability and the effects of EPCs after transplantation. A rat ALI model will be used, and the study will be present at cell, tissue and animal model levels. The detail signaling pathways and mechanisms will be researched.AS an active phospholipids without immunocompetence, LPA can be used in a wide range of applications for the key link that antiapoptotic without differentiation in EPCs transplantation treatment of ALI. The objective of the study is exploring and expounding this application prospect.

英文关键词： lysophosphatidic acid;endothlial progenitor cells;acute lung injury;stem cell transplatation;signalling pathway