冠状动脉微栓塞所致的心肌重构严重影响冠心病介入治疗的预后。细胞外基质（ECM）合成/降解失平衡是心肌重构的关键。既往研究发现微小RNA（miRs）调控ECM的表达，然而，miRs能否调控微栓塞后多种ECM的再平衡尚不明确。我们前期研究发现，冠脉微栓塞后肿瘤坏死因子α（TNF-α）和miR-125b表达升高；TNF-α体外刺激成纤维细胞，不仅上调miR125b、促进胶原合成，还能促进ECM降解相关蛋白酶（MMPs）的分泌。因此推测，调控miR-125b的表达可以改善微栓塞后心肌重构。本项目拟构建差异性表达miR-125b的冠脉微栓塞小鼠模型和离体成纤维细胞，从成纤维细胞增殖分化、基质合成、基质降解三方面，探索miR-125b不同时相表达对ECM动态合成/降解再平衡的影响。软件预测并以双荧光素酶报告验证miR-125b靶基因，明确信号通路。进而，为临床防治冠状动脉微栓塞后的心肌重构提供新思路。

Cardiac remodeling induced by coronary microembolization significantly infulence the clinical prognosis of coronary artery disease after coronary intervention.Synthesis and degradation loss-balance of extracellular matrix plays a critical role in post-injury cardiac remodeling.Presious studies indicatied that microRNA might be involved in regulation of extracellular matrix. However,it is unclear about its effect and detailed mechanism on post-coronary microembolization.Our polit study found that tumor necrosis factor-α(TNF-α) and miR-125b were increased after coronary microembolization. Meanwihle,cardiac fibroblast stimulated by TNF-α,not only upregulated expresssion of miR-125b and synthesis of collagen, but also increased the level of matrix metallopreteinases. Therefore, we supposed that different expressed miR-125b could modulate the re-balance of extracellular matrix after coronary microembolization and improved cardiac remodeling. In this study, mice coronary microembolization model and cardiac fibroblast with differential expression of miR-125b were developed. Then, we try to find out the detailed mechanism between miR-125b and dynamic response of extracellular matrix from the fields of cell differentiation, matrix synthesis and degradation. Meanwhile, luciferase report is applied to document the target genes and signal transduction of miR-125b. Above all, These fingdings will provide novel evidence for clinical treatment of coronary microembolization.