Bone Marrow Mesenchymal Stem Cell Overexpressing miR-486-5p Protect Hypoxic-Injured Cardiomyocytes via Exosomes
Objective To investigate the effects and mechanisms of exosomes(Exo)derived from bone marrow mesenchymal stem cell(BMSC)in mice overexpressing mi R-486-5 p on hypoxic-injured cardiomyocytes.Methods Mouse BMSC overexpressing miR-486-5p was constructed by lentivirus transfection.Exo secreted by successfully transfected BMSC were extracted,including Exo secreted by empty carrier BMSC(Exo-NC),Exo secreted by BMSC overexpressing miR-486-5p(Exo-miR-486),and Exo secreted by untreated BMSC(Exo-Control).Primary cardiomyocytes from 12～18 d fetal rats were divided into normal oxygen culture group(Normoxia group),hypoxia culture group(Hypoxia group),Hypoxia+Exo-NC group and Hypoxia+Exo-miR-486 group,and were given hypoxia treatments for different times to stimulate the hypoxic state of cardiomyocytes.Cell proliferation,apoptosis rate,and the expression levels of reactive oxygen species(ROS),nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),and cleaved caspase-1 were examined.Results The proliferation of cardiomyocytes in Hypoxia group was lower than that in Normoxia group,while the apoptosis rate and the expression levels of ROS,NLRP3 and cleaved caspase-1 in Hypoxia group were higher than those in Normoxia group(P＜0.05);Myocardial cell proliferation capacity in Hypoxia+Exo-NC group was higher than that in Hypoxia group,the apoptosis rate and the expression levels of ROS,NLRP3 and cleaved caspase-1 were lower than those in Hypoxia group(P＜0.05);The proliferation ability of myocardial cells in Hypoxia+Exo-miR-486 group was higher than that in Hypoxia+Exo-NC group,and the apoptosis rate and the expression levels of ROS,NLRP3 and cleaved caspase-1 were lower than those in Hypoxia+Exo-NC group(P＜0.05).Conclusion Exo from BMSC overexpressing with miR-486-5p can reduce hypoxic-induced ROS production and apoptosis of cardiomyocytes,and ameliorate hypoxic-induced slow proliferation of cardiomyocytes.
Bone marrow mesenchymal stem cellExosomeMyocardial hypoxiamiR-486-5pApoptosis
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维普
