急性肺损伤(ALI)主要发病原因是肺泡上皮细胞及毛细血管内皮细胞损伤。肺内源间充质干细胞(LR-MSC)可通过旁分泌或分化为上皮细胞修复肺组织。但LR-MSC数量少，其修复机制仍有待确定。研究发现，肺移植后支气管肺泡灌洗内溶血磷脂酸（LPA）与LR-MSC的数量都提高，体外LPA/ LPAR1通过β-catenin信号通路诱导LR-MSC迁移，而LR-MSC迁移对肺组织修复至关重要。LPA是活性磷脂，通过膜上的G蛋白偶联受体提高多种细胞增殖迁移活性。前期研究中我们也发现，LPA促进人脐带间充质干细胞，大鼠骨髓分离的内皮祖细胞的增殖，并促进肿瘤细胞的迁移。因此，该课题中拟复制大鼠ALI模型，从细胞-组织-动物层次研究LPA对LR-MSC存活，迁移活性及修复ALI的影响，并阐明其详细的信号转导机制。LPA在促进病体内源性LR-MSC迁移进而治疗ALI中显示出广泛的应用前景。

The injury of alveolar epithelial cell and capillary endothelial cell are key points of acute lung injury(ALI).Lung resident mesenchymal stem cells (LR - MSC) repair the injury in lung through paracrine or differentiation into lung epithelial cells. However, LR-MSCs in adult lung are very low numbers and its mechanism remains to be determined. The study found that LPA levels were increased in bronchoalveolar lavage (BAL) of human lung allografts with increasing numbers of LR-MSC. lysophosphatidic acid (LPA) plays a principal role in the migration of human LR-MSCs through a signaling pathway involving LPA1-induced b-catenin activation. LR-MSCs migration is considered to be an important first step in lung injury. LPA is bioactive lipid, which promote migration and proliferation activity of a variety of cells through G protein coupled receptors on the membranes. In previous research, we also found that LPA promote the proliferation of human umbilical cord mesenchymal stem cells and endothelial progenitor cells derived from rat bone marrow, and increase the migration of cancer cells.Therefore, we are intending to study the functions of LPA on LR-MSCs survival rate, migration ability and the effects of ALI repair. 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 on LR - MSC migration and treating ALI. The objective of the study is exploring and expounding this application prospect.