炎症反应对急性心梗（AMI）后心室重构尤为关键。间质干细胞（MSC）具旁分泌与免疫调节特性，是干预心室重构理想工具，但因难以有效靶向病灶，疗效并不稳定。申请人发现较之骨髓MSC，心脏MSC的AMI疗效更佳，核心机制或是其更充分的靶向病灶能力。表达谱分析发现心脏MSC的靶向能力相关受体中，P2Y1表达最高，其在骨髓MSC表达则极低。心损释放的ATP具趋化作用，招募细胞靶向病灶，P2Y1正是其特异受体。本研究拟在前期基础上，通过受体拮抗、细胞改造、梯度及细胞膜动力学、轨迹分析、蛋白检测等技术，明确P2Y1介导的心脏MSC靶向作用，阐明其与接受趋化信号、放大趋化信号、提高细胞运动能力等三方面间关系，确定其在心脏MSC治疗AMI的作用机制；评估过表达P2Y1骨髓MSC的AMI疗效，进一步确证其作用。本研究不仅阐明P2Y1的心脏MSC治疗AMI作用机制，而且为推进MSC的AMI临床应用奠定坚实基础。

Acute myocardial infarction (AMI) has become an important disease threatening human health in China. It is crucial to cure AMI that how to control ventricular remodeling, which is still one of the biggest obstacles of AMI interventions. It is well known that inflammation could play a key role in the progress of ventricular remodeling. The activities of mesenchymal stem cells (MSCs) about immunomodulation, inducing angiogenesis and nutrition support make it ideal for controlling ventricular remodeling, curing heart failure and solving the dilemma of clinic therapy of AMI. However, the therapeutic effect of MSCs on AMI is not stable, since the lacking ability of MSCs to target lesions. How to enhance the lesions targeting ability of MSCs to stabilize their therapeutic effect on AMI should be key to promoting the clinical application of MSCs in AMI. We have demonstrated that the lesions targeting ability of cardiac MSCs (cMSCs) is significantly stronger than bone marrow MSCs (bmMSCs). It made cMSCs to target lesions more efficiently than bmMSCs. Consequently, cMSCs could be more effective to control ventricular remodeling, compared with bmMSCs. The results of RNA-sequencing indicated that purinoceptor P2Y1 was the highest expressing receptor involving in lesions-targeting in cMSCs. However, its expression of bmMSCs was extremely low. ATP releasing would be increased significantly during myocardial infarction. It has been well-known that ATP is a chemoattractant signal, which could recruit stem cells, immunocytes and endotheliocytes into lesions. P2Y1 is one of the specific receptors of ATP. Based on our previous reports and recent progress, we are going to investigate the role of P2Y1 in ATP mediated targeting of cMSCs. Furthermore, we are going to clarify how P2Y1 could enhance the ability of MSCs to target lesions, which mechanism might include receiving, magnifying and transmitting of chemoattractant signal, and cell movement. In order to further confirm the therapeutic effect of MSCs via purinoceptor P2Y1 on AMI, we decide to study whether enhancing the lesions targeting ability of bmMSCs via over-expressing P2Y1 could optimize their therapeutic effect on AMI mouse. Our findings not only will expound the therapeutic mechanism of cMSCs on acute myocardial infarction via purinoceptor P2Y1, but also will provide a steady base in theory and technology for promoting clinical application of MSCs for AMI.