TRPA1促血管生成调控梗死后心肌重构的作用及机制研究

心肌梗死是严重威胁人类健康的疾病，心梗后心肌重构的防治是当前亟待解决的问题。内皮祖细胞（EPC）介导的血管新生可挽救缺血心肌，抑制心肌的不良重构。前期研究中发现，激活瞬时受体电位通道蛋白A1（TRPA1）可增强EPC的增殖和迁移能力，TRPA 1敲基因小鼠的梗死周围新生血管减少。据此，我们推测：心梗后的炎症、氧化应激可激活TRPA1，TRPA1通过促进EPC的动员、增殖和迁移，促进血管新生，从而改善心梗后心肌重构。本项目拟选用TRPA1敲基因小鼠为工具，构建心肌梗死的模型和EPC血管新生模型，探讨TRPA1在梗死后心肌重构中的作用；以EPC的动员、增殖和迁移与血管新生为切入点，探讨TRPA1调控梗死后心肌重构的机制。以期揭示TRPA1在梗死后心肌重构中的作用，阐明其调节机制，为梗死后心肌重构的防治提供新思路。

Myocardial infarction is a serious threat to both life and health. And it is an important task to prevent post-infarction remodeling. Endothelial progenitor cell (EPC) mediated angiogenesis could rescue ischemic myocardium and protects the heart against adverse remodeling. In our previous work, we have identified activation of transient receptor potential ankyrin subfamily member 1 (TRPA 1) could promote EPC proliferation and migration in vitro. In addition, capillary density was reduced in TRPV1-deficient mice as compared to WT mice. Hence, we speculate that TRPA1 could be activated by the inflammation and oxidation stress after myocardial infarction, which might promote EPC mobilization, proliferation and migration. Furthermore, EPC mediated angiogenesis could ameliorate post-infarction remodeling. In our study, we are going to reveal the role of TRPA1 in post-infarction remodeling by using TRPA1-deficient mice, myocardial infarction model and angiogenesis model. What's more, we will research the mechanisms of TRPA1 regulating post-infarction remodeling via focusing on EPC mobilization, proliferation and migration and angiogenesis. The results will give us new ideas for exploring novel role of TRPA1 and treament of ischemic diseases.