Abstract: Objective:To investigate the effect of miR-425-5p and its downstream target HSPB8 on myocardial ischemia-reperfusion injury (MIRI) and the related mechanisms.Methods:AC16 cells were randomly divided into control group, H/R group, H/R+miR-NC group, H/R+miR-425-5p inhibitor group, H/R+miR-425-5p mimic group, H/R+OE-NC group, and H/R+OE-HSPB8 group.The proliferation capacity of AC16 was determined by cell counting kit-8 (CCK-8) method.The levels of superoxide dismutase (SOD), malonaldehyde (MDA), tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 were detected by enzyme-linked immunosorbent assay(ELISA).The RNA and protein expression of Caspase-3, Bax and Bcl-2 was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting.The targeting relationship between miR-425-5p and HSPB8 was verified by luciferase reporter gene.Results:The expression of miR-425-5p in patients with MIRI was significantly higher than that in the normal population, and the expression of HSPB8 in patients with MIRI was significantly lower than that in the normal population.Compared with the control group, the cell viability of H/R group, H/R+miR-NC group, H/R+miR-425-5p mimic group, and H/R+OE-NC group decreased(P< 0.01)and apoptosis, inflammation as well as oxidative stress levels increased(P< 0.01).Compared with the control group, the cell viability of H/R+miR-425-5p inhibitor group and H/R+OE-HSPB8 inhibitor group significantly increased (P< 0.01) and apoptosis, inflammation as well as oxidative stress levels decreased (P< 0.01).Compared with the H/R+OE-NC group, apoptosis, inflammation as well as oxidative stress levels in the H/R+OEHSPB8 group significantly decreased(P< 0.01).The results of targeting relationship showed that there was a targeting relationship between miR-425-5p and HSPB8.Conclusion:miR-425-5p can target HSPB8 to mediate MIRI, and inhibition of miR-425-5p can reduce MIRI by up-regulation of HSPB8.