Study on the Protective Effects and Mechanisms of Parthenolide Against Doxorubicin-Induced H9c2 Cardiomyocyte Injury
Objective To investigate the protective mechanism of parthenolide(PTL)against doxorubicin(DOX)-induced cardiomyocyte injury.Methods Rat H9c2 cardiomyocytes were cultured,and then the optimal concentration of DOX and PTL was determined by CCK-8 assay.Rat H9c2 cardiomyocytes were randomly divided into control group,PTL group,DOX group and DOX+PTL group.Intracellular reactive oxygen species levels were detected with DCFH-DA using a flow cytometer and the apoptotic cells were measured with Annexin V-FITC/PI staining kit by flow cytometer.Western blot was employed to detect the expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),B-cell lymphoma-2-associated X protein(Bax)and B-cell lymphoma-2(Bcl-2).Results The cell viability of H9c2 cardiomyocytes exposed to 0.5～5.0 μmol/L DOX for 24 h decreased in a dose-dependent effect(P＜0.05),and 1.0μmol/L DOX could reduce the viability of H9c2 cardiomyocytes to 53.0％±0.4％.The cell viability of H9c2 cardiomyocytes pretreated with 5.0 μmol/L PTL for 3 h was significantly increased after exposure to DOX(P＜0.05).The protein expression levels of Nrf2,HO-l and Bcl-2 in DOX group were significantly decreased comparing with the control group,while the proapoptotic protein Bax was significantly increased(P＜0.05),and the level of oxidative stress and the proportion of apoptosis were increased(P＜0.05).Contrasted with DOX group,pretreatment with PTL could significantly increase the expression levels of Nrf2,HO-1 and Bcl-2 protein,and reduce the expression level of Bax(P＜0.05),and decrease the degree of oxidative stress and apoptosis rate of DOX-induced H9c2 cardiomyocytes(P＜0.05).Conclusion PTL alleviates DOX-induced injury of H9c2 cardiomyocytes which was associated with activation of Nrf2/HO-1 pathway and inhibition of Bcl-2/Bax signaling pathway.
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维普
