Objective To investigate the molecular mechanism of miR-126-EPC-MPs in ameliorating oxygen glucose deprivation/reoxygenation (OGD/R) injury in cardiomyocytes.Methods The cardiomyocytes were used to establish the control and OGD/R injury models,and EPC-MPs and miR-126 mimic EPC-MPs treatments were administered respectively.The structural changes in cardiomyocyte organelles were assessed by transmission electron microscopy.ELISA was used to detect the expression levels of IL-6,TNF-α and HMGB-1 in cardiomyocytes.The protein and mRNA expression levels of Ang Ⅱ,caspase-6,eNOS,FOXO1,MPO,NF-κB,ERK1,LKB1,SIRT1,GRP78,GM130 and PGC-1α in cardiomyocytes after different treatments were detected by Western blot and quantitative PCR.Results The mitochondria structure in some cardiomyo-cytes of the OGD/R+miR-126 mimic EPC-MPs group was complete,the size of some mitochondria was in-creased,the surface of the endoplasmic reticulum had fewer ribosomes,and some of the Golgi vesicles gath-ered.Compared with the OGD/R+EPC-MPs group,the expression levels of IL-6,TNF-α and HMGB-1 in the OGD/R+miR-126 mimic EPC-MPs group were down-regulated.Compared with the OGD/R+EPC-MPs group,the expression levels of Ang Ⅱ,caspase-6,p-ERK1/2 and GRP78 protein in the OGD/R+miR-126 mimic EPC-MPs group were down-regulated,and the expression levels of p-LKB1,GM130 and PGC-1α protein in the OGD/R+miR-126 mimic EPC-MPs group were up-regulated.The quantitative PCR(qPCR) results showed that compared with the OGD/R+EPC-MPs group,the expression levels of Ang Ⅱ,MPO and GRP78 in the OGD/R+miR-126 mimic EPC-MPs group were down-regulated,and the expression levels of eNOS,GM130 and PGC-1α were up-regulated.Conclusion When OGD/R injury occurs in cardiomyocytes,miR-126 mimic EPC-MPs regulates PGC-1α/GM130 expression and inhibits Ang Ⅱ-induced stress injury response,thereby reduces the OGD/R damage in cardiomyocytes.