Abstract: Objective To investigate the protective effect and molecular mechanism of bone marrow mesenchymal stem cells(BM-MSCs)-derived exosomes against anoxia-reoxygenation (A/R) injury in rat cardiomyoblast cell line H9c2. Methods The A/R injury model of H9c2 cells was constructed. Electron microscopy and Western blot were used to identify BM-MSCs-derived exosomes(BM-MSCs-exos); PHK26 red fluorescence-labeled exosomes were used to observe the endocytosis of H9c2 cells; CCK-8 assay was used to detect cell viability; EdU cell proliferation assay was used to detect cell proliferation ability; Ferroptosis-related detection kits were used to determine Fe²⁺, MDA, GSH content; Flow cytometry was used to detect reactive oxygen species free radical ROS level. Results BM-MSCs-exos were successfully identified, and the endocytosis of BM-MSCs-exos by H9c2 cells was found. Compared with A/R group, cell viability and proliferation in A/R+ MSCs-exo group were significantly improved (P＜0.05).Ferroptosis marker protein GPX4, SLC7A11 increased; Transferrin receptor TFR1 expression decreased(P＜0.05); And Fe²⁺ ions, MDA, ROS all decreased while GSH increased(P＜0.05). After treatment with the ferroptosis inducer Erastin, the protective effect of BM-MSCs-exo against A/R injury in H9c2 cells was significantly reduced (P＜0.05). Conclusions BM-MSCs-exos can alleviate A/R-induced cardiomyocyte injury, and is potentially mediated by inhibiting cardiomyocyte ferroptosis.

Key words: exosomes, ferroptosis, cardiomyoblast cell line H9c2, anoxia-reoxygenation