哮喘骨髓间充质干细胞"归巢"新途径:miR-139/Notch1轴调控巨噬细胞极化OA

Objective To observe the expression of miR-139/Notch1 axis and macrophage polarization in the hom-ing changes of bone mesenchymal stem cells(BMSCs)in asthmatic rats,and to explore the possible mechanism of immune regulation by BMSCs during asthma.Methods 30 male SD rats were randomly divided into three groups:normal control group,model control group and BMSCs implantation group,with 10 rats in each group.BMSCs la-beled with CFSE were infused into the body of asthmatic rats through the tail vein,and the homing status of BMSCs in asthmatic lung tissue was detected by flow cytometry.Changes in the proportion of inflammatory cells in alveolar lavage fluid were detected by Wright-Giemsa Stain;the levels of macrophage polarization cytokines IFN-γ,IL-13,CD80 and CD206 in rat serum were detected by ELISA;the miR-139,Notch1,NOS2,Arg1 and CXCR4 in lung tissue were detected by RT-qPCR.Results Compared with the NC group,the expression of serum CD80 and IFN-γ in the MC group decreased,while the expression of IL-13 and CD206 increased(P<0.01).The expression of miR-139 in lung tissue of MC group rats decreased,and the expression of macrophage polarization markers NOS2,Arg1,and homing marker CXCR4 genes increased(P<0.01).Compared with the MC group,the expression of IFN-γ of rats in BMSCs group increased,while the expression of IL-13 and CD206 decreased(P<0.01).The ex-pression of miR-139,CXCR4,and SDF-1 mRNA in the lung tissue of rats of BMSCs group increased,while the ex-pression of Notch1,NOS2,and Arg1 decreased(P<0.01).Correlation analysis showed that CXCR4 was positively correlated with miR-139(P<0.05),while CXCR4 was negatively correlated with Notch1(P<0.05).SDF-1 and IFN-γ was a positively correlated(P<0.05),while SDF-1 was negatively correlated with Arg1 and CD206(P<0.05).Conclusion The miR-139/Notch1 axis can promote BMCs homing in asthmatic rats by affecting macro-phage polarization in asthma.