基于循环外泌体myomiRs调控Notch3/CXCR4动员内皮祖细胞靶向归巢和分化探讨麝香保心丸促梗死后心肌再生的机制

益气温通可促精气血运化，其经典方剂麝香保心丸（SBP）也发现可促进精气血化生介导的心肌血管再生，但机制不清。前期发现SBP可上调心梗后循环外泌体心肌源性miRNAs（myomiRs）并与动员内皮祖细胞（EPC）有关，myomiRs则发现可通过Notch/CXCR4促进干细胞动员及向心肌分化。故提出假说：SBP可通过循环外泌体myomiRs调控Notch3/CXCR4动员骨髓EPC靶向归巢和分化并促进梗死后心肌再生。课题拟临床检测并建立心肌梗死小鼠和培养EPC模型，以外泌体miRNA芯片检测及miRNA转染等探讨循环外泌体myomiRs远程介导EPC参与心肌再生及SBP通过myomiRs/Notch3/CXCR4促进EPC动员、归巢、分化及梗死后心肌再生的作用和机制。项目将以传统中医理论与最新生物学技术相结合去阐释SBP促心肌再生机制，从全新的视角探讨促精气血化生和心肌重建的新策略和新靶点。

Yiqi Wentong, as a classic treatment of traditional Chinese medicine, can promote the circulation and metaplasia of Qi and blood.With replenishing Qi and warming blood effect, Shexiang Baoxin Pill (SBP) can promote myocardial regeneration after infarction, but the mechanism is unclear. Some studies have shown that SBP is related to promoting mobilization and homing of endothelial progenitor cells (EPCs), and it has been found early that SBP can up-regulate circulating exocrine myomiRs after myocardial infarction, while myomiRs can induce myocardial differentiation and promote cell mobilization through Notch3/CXCR4. Therefore, a hypothesis has been put forward: SBP can regulate Notch3/CXCR4 to mobilize bone marrow EPCs to target homing and differentiation and promote regeneration of infarcted myocardium through circulating exocrine myomiRs. The subject intends to clinically detect and establish myocardial infarction mice and culture EPCs models, and to explore the changes of circulating exocrine myomiR after myocardial infarction and role and mechanism of SBP in promoting EPCs mobilization, homing, differentiation and regeneration of infarcted myocardium through myomiRs/Notch3/ CXCR4 used by detection of exosomes miR chip and miRNA transfection. The study combines traditional Chinese medicine and molecular biology techniques to explore the mechanism of SBP promoting " Metaplasia of essence, Qi and blood ", and will explore the new intervention strategies and targets of myocardial regeneration and stem cell treatment from a new perspective.