Objective:The nuclear factor erythroid 2(NFE2)-related factor 2(Nrf2)is associated with doxorubicin(DOX)-induced cardiac injury.It has been reported that microRNA-24-3p(miR-24-3p)may regulate the Keapl by mRNA degradation,whereas Keapl can suppress the activation of Nrf2.However,the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.Methods:The mice receiving DOX were used as cardiac injury model.In this study,an adeno-associated virus 9 system was used to deliver miR-24-3p or miR-scramble to mice hearts.The echocardiographic and hemodynamic analyses were used to evaluate the effects of miR-24-3p on cardiac function under DOX stimulation.ELISA and RT-PCR were used to detect protein or mRNA expressions associated with cardiac injury,inflammation response,apoptosis and oxidative stress.Western Blot were used for quantitative analysis of the roles of miR-24-3p in regulating Nrf2 expression.H9C2 cells used to verify the role of miR-24-3p in vitro.Results:We found that miR-24-3p mRNA was significantly decreased in DOX-treated mice and cardiomyocytes.Overexpression of miR-24-3p blocked cardiac injury caused by DOX injection,as reflected by the reduction in the levels of cardiac troponin Ⅰ,creatinine kinase isoenzyme MB and the N-terminal pro brain natriuretic peptide.Furthermore,miR-24-3p reduced oxidative stress and cell loss without affecting the inflammation response.As expected,we found that Nrf2 was upregulated by miR-24-3p supplementation,and that the protective efforts of miR-24-3p supplementation were abolished when Nrf2 was silenced.Conclusion:The results from this study suggest that miR-24-3p protects cardiomyocytes against DOX-induced heart injury via activation of the Nrf2 pathway.miR-24-3p supplementation may be a novel strategy to counteract the cardiac side effects of DOX treatment.