Influence Of Carvedilol On Apoptosis And Expression Of Bcl-2/Bax Protein Of Cultured Cardiomyocytes Infected By Coxsackievirus B3

ObjectivesTo investigate the effects of carvedilol on apoptosis and expression of Bcl-2/Bax protein of cultured cardiomyocytes infected by Coxsackievirus B3(CVB3).MethodsCardiomyocytes derived from neonatal Wistar rats were purified by differential adhesion method. There were four groups:CVB3 group, Carvedilol group, Metoprolol group and normal control group. The cardiomyocytes of the first three groups were infected by CVB3 and then added by serum-free DMED, Carvedilol media, Metoprolol media, respectively. The cardiomyocytes in Normal control group were added by serum-free DMED. The histopathologic changes and rhythmical beat of cardiomyocytes were observed by inverted phase contrast. The change of cardiomyocytes morphology shape were observed with electrical microscope.Superoxide dismutase(SOD)activity and Malondialdehyde(MDA) content in the culture media were measured by xanthine oxidase method and thiobarbituric acid method, respectively. Chemiluminescentimmunoassay were used to perform the CardiacTroponinT(cTnT) content in the culture media.Flow cytometry was used to detect Cardiomyocytes apoptosis. The expression of Bcl-2 and Bax protein in cardiomyocytes were determined by immunocytochemistry. Results1. Compared with CVB3 group, the beating rate of the Cardiomyocytes (96.00±11.22 vs.36.40±12.76) and SOD activity in the culture media (57.37±11.84 vs. 41.12±2.45) were significantly increased (P both<0.05), MDA content (2.19±1.63 vs. 7.13±1.68) and cTnT content (5.19±1.81 vs.10.86±0.9) in the culture media were significantly reduced in Carvedilol group (P both<0.05),Cardiomyocytes apoptosis (38.4±7.12 vs.21.1±4.00) also reduced in Carvedilol group (P<0.05).There were no significant differences in the beating rate (44.20±9.76 vs.36.40±12.76), cardiomyocytes apoptosis (32.67±1.02 vs.38.4±7.12), SOD activity (42.77±6.31 vs. 41.12±2.45), MDA content (6.76±2.74 vs.7.13±1.68),and cTnT content (5.19±1.81 vs.10.86±0.9) between the metoprolol group and the CVB3 group (P>0.05)2. The expression of Bcl-2 protein of cardiomyocyte in Carvedilol group was stronger than that of CVB3 group and metoprolol group, while the expression of Bax protein of cardiomyocyte was significantly reduced.ConclusionCarvedilol is effective in inhibiting apoptosis of CVB3-infected cultured cardiomyocytes, which might be due to its antioxidation capacity, upregulation of Bcl-2 and downregulation of Bax of cardiomyocytes.