Abstract： Objective To investigate the protective mechanism of mitochonic acid 5(MA5)against doxorubicin(DOX)-induced cardiomyocyte injury.Methods H9c2 cells treated with DOX were used as the model of cell injury.The cells were divided into CON group(normal group),DOX group(cardiomyocytes were treated with 1 μmol/L DOX for 24 h),DOX+MA5 group[cardiomyocytes were treated with 1 μmol/L DOX+MA5(1 μmol/L,5 μmol/L,and 10μmol/L)for 24 hours]and MA5 group(MA5 was added to cardiomyocytes for 24 h).Protein expression levels of apopto-sis(Bax,Bel-2,cleaved caspase3,cleaved caspase9),pyroptosis(NLRP3,caspase 1,interleukin(IL)-18),and inflammation[nuclear factor-κB(NF-κB),tumor necrosis factor-α(TNF-α),IL-1 β,IL-6]related markers were detected using western blotting.Results Compared to the CON group,the DOX group showed upregulated expres-sion of inflammation-related proteins(NF-κB,TNF-α,IL-1 β,IL-6).After treatment with MA5(5,10 μmol/L),the expression of inflammation-related proteins was significantly inhibited(P＜0.05).The expression levels of py-roptosis-related proteins(NLRP3、Caspase-1、IL-18)in the DOX group were significantly higher than those in the CON group(P＜0.05).However,after treatment with MA5(5,10 μmol/L),the expression levels of pyroptosis-relat-ed proteins were significantly reduced(P＜0.05),while pro-apoptotic protein expression was decreased(P＜0.05)and anti-apoptotic protein expression was increased(P＜0.05).Conclusion MA5 may exert protective effects against DOX-induced cardiotoxicity by inhibiting cell inflammation,pyroptosis,and apoptosis.