关键词: SIRT6; 缺氧/复氧; 凋亡; 心肌细胞; RNA干扰

Abstract: Objective To explore the effect of inhibiting intracellular SIRT6 gene expression in H9C2 cardiomyocytes by RNA interference technology on cell injure induced by anoxia/reoxygenation(A/R) and its mechanism.Methods H9C2 cardiomyocytes were randomly divided into control(Con) group,A/R group,negative control(NC) group and SIRT6-shRNA plasmid treated group(shRNA group).Survival rate,apoptotic rate,Caspase-3 activity,expression levels of SIRT6,nuclear factor(NF)-κBp65,I-κBα and interleukin(IL)-6 and tumor necrosis factor(TNF)-α in culture medium of H9C2 cardiomyocytes in four groups were assessed and compared.Results Compared with Con group,survival rate of H9C2 cardiomyocytes and the expression level of I-κBα protein in cytoplasm decreased significantly in A/R group,apoptotic rate of H9C2 cardiomyocytes,expression levels of SIRT6 mRNA and protein,NF-κBp65 protein in nucleus,IL-6,TNF-α in culture medium and Caspase-3 activity increased significantly in A/R group（P<0.05）.Compared with A/R group,survival rate of H9C2 cardiomyocytes,expression levels of SIRT6 mRNA and protein and I-κBα protein in cytoplasm decreased significantly in shRNA group,while apoptotic rate of H9C2 cardiomyocytes,expression levels of NF-κBp65 protein in nucleus,IL-6,TNF-α in culture medium and Caspase-3 activity increased significantly in shRNA group（P<0.05）.Conclusion Inhibition of intracellular SIRT6 gene expression in H9C2 cardiomyocytes can promote the secretion of inflammatory cytokines,activate NF-κB signaling pathway,induce cell apoptosis and aggravate cardiomyocytes injury induced by A/R.

Key words: SIRT6; Anoxia/reoxygenation; Apoptosis; Cardiomyocytes; RNA interference