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.

Di FAN;Hong-bin CHEN;Yan LENG;Shi-jun YANG

Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Pulmonary and Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430060,China

当代医学科学(英文)

[1]Di FAN;Hong-bin CHEN;Yan LENG;Shi-jun YANG-.MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice)[J].当代医学科学(英文),2022(01):48-55

NFE2

MiR,3p,Attenuates,Doxorubicin,induced,Cardiotoxicity,via,Nrf2,Pathway,Mice,Objective,nuclear,erythroid,related,associated,doxorubicin,DOX,cardiac,injury,It,has,been,reported,that,microRNA,miR,may,Keapl,by,degradation,whereas,suppress,activation,However,cardiotoxicity,remains,unclear,Methods,mice,receiving,were,model,In,this,study,adeno,virus,system,was,deliver,scramble,hearts,echocardiographic,hemodynamic,analyses,evaluate,effects,function,under,stimulation,detect,protein,expressions,inflammation,response,apoptosis,oxidative,stress,Blot,quantitative,analysis,roles,regulating,H9C2,cells,verify,vitro,Results,found,significantly,decreased,treated,cardiomyocytes,Overexpression,blocked,caused,injection,reflected,reduction,levels,troponin,creatinine,kinase,isoenzyme,MB,terminal,brain,natriuretic,peptide,Furthermore,reduced,loss,without,affecting,expected,upregulated,supplementation,protective,efforts,abolished,when,silenced,Conclusion,results,from,suggest,protects,against,pathway,novel,strategy,counteract,side,treatment

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