Irisin-pretreated BMMSCs secrete exosomes to alleviate cardiomyocytes pyroptosis and oxidative stress to hypoxia/reoxygenation injury.

BACKGROUND More effective strategies to improve myocardial ischemia/reperfusion (MI/R) injury is underdetermined. The cardiomyocytes pyroptosis and bone marrow-derived mesenchymal stem cells (BMMSCs) have been well considered as novel therapies to attenuate MI/R injury, however, the relationship has not yet been determined. OBJECTIVE We aims to clear whether pre-treatment BMMSCs to protect against MI/R injury by repressing cardiomyocytes pyroptosis, as well as to further elucidate the potential mechanisms. METHODS Cardiomyocytes were treated with hypoxia followed by reoxygenation to mimic MI/R injury. Pre-treatment BMMSCs or its exosomes were co-cultured with cardiomyocytes following to hypoxia/reoxygenation(H/R). Cell Counting Kit-8 (CCK-8) assay was used to determine cell viability. ROS production was determined by dihydroethidium (DHE) stain. Enzyme-linked immunosorbent assay (ELISA) were used to detect IL-1β and IL-18. RESULTS We indicated that Irisin pre-treatment BMMSCs (Irisin-BMMSCs) protected cardiomyocytes against hypoxia/reoxygenation(H/R)-induced injuries. The underlying molecular mechanism was further identified. Irisin-BMMSCs were found to secrete exosomes, which repressed cardiomyocytes pyroptosis and oxidative stress response by suppressing NLRP3 under H/R condition. CONCLUSION Based on our findings, we revealed a promising target that exosomes derived from BMMSCs with Irisin pre-treatment to elevate the therapeutic benefits for the H/R injury.

背景 改善心肌缺血/再灌注（MI/R）损伤的更有效的策略是不确定的。尚未确定。 客观的 我们旨在清除治疗前BMMSC是否通过反映心肌细胞的凋亡来防止MI/R损伤，并进一步阐明潜在的机制。 方法 用缺氧处理心肌细胞，然后再氧化为MIMIC MI/R损伤。 ROS的产生是通过二氢乙烯（DHE）染色确定的。 IL-18。 结果 我们指出，虹膜疗法BMMSC（Irisin-BMMSCs）可保护心肌细胞免受缺氧/重氧（H/R）诱导的损伤。通过在H/R条件下抑制NLRP3，氧化应激反应。 结论 根据我们的发现，我们揭示了一个有望的靶标，即从BMMSC衍生出具有IRISIN预处理的外泌体，以提高H/R损伤的治疗益处。