Effect of valsartan on hypoxia-reoxygenation induced cardiomyocyte pyroptosis by regulating the ROS/NLRP3/caspase-1 signaling pathway
Objective To investigate the effect of valsartan(VAL)on hypoxia/reoxygenation(H/R)induced cardiomyocyte py-roptosis by regulating the reactive oxygen species(ROS)/nucleotide binding oligomeric domain like receptor protein 3(NLRP3)/cas-pase-1 signaling pathway.Methods After being treated with 0.1～3.2 μmol/L valsartan,H9C2 cells were treated with H/R,cell ac-tivity was measured by MTT assay,and the optimal concentration of valsartan was selected.H9C2 cells were divided into control group,H/R group,valsartan low,medium and high concentration groups(VAL-L group,VAL-M group,VAL-H group),and valsartan high con-centration+ROS activator group(VAL-H+TMAO group).JC-1 staining method was applied to detect the level of mitochondrial mem-brane potential(MMP).ELISA method was applied to detect the contents of malondialdehyde(MDA),superoxide dismutase(SOD),lactate dehydrogenase(LDH)and reactive oxygen species(ROS)in H9C2 cells.Western blot was applied to detect the expression of IL-1β,IL-18,NLRP3,caspase-1 protein.Results Valsartan at concentrations of 0.1-3.2 μmol/L was able to promote H/R induced prolifer-ation of H9C2 cells.Valsartan concentrations of 0.4 μmol/L,0.8 μmol/L,and 1.6 μmol/L were selected for the experiment.Compared with Control group,the positive rates of ROS,LDH,MDA and PI,the expression levels of IL-1 β,IL-18,ROS,NLRP3 and caspase-1 in H/R group were significantly increased,and the levels of MMP and SOD were decreased(P＜0.001).Compared with H/R group,the positive rates of ROS,LDH,MDA and PI,the expression levels of IL-1β,IL-18,ROS,NLRP3 and caspase-1 in H9C2 cells in VAL-L,VAL-M and VAL-H groups were decreased,while the levels of MMP and SOD were increased(P＜0.001).Compared with VAL-H group,the positive rates of ROS,LDH,MDA,PI,IL-1β,IL-18,ROS,NLRP3 and caspase-1 in H9C2 cells in VAL-H+TMAO group were significantly in-creased,while the levels of MMP and SOD were decreased(P＜0.001).Conclusion Valsartan may inhibit ROS/NLRP3/caspase-1 signaling pathway and inhibit H/R-induced cardiomyocyte pyroptosis.
cardiomyocytesvalsartanreactive oxygen species(ROS)/nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)/caspase-1hypoxia/reoxygenationpyroptosis
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