Effects of sacubitril valsartan on mitochondrial dynamics and cell apoptosis in hypoxic cardiomyocytes
Objective To verify whether sacubitril valsartan(S/V)can ameliorate the apoptosis level of hypoxic H9c2 cardiomyo-cytes by regulating mitochondrial dynamic system,and exert cardioprotective effects.Methods H9c2 cardiomyocytes were cultured and established a glucose oxygen deprivation model(OGD).The cells were divided into three groups:control group(CON),model group(OGD),S/V group(S/V).Apoptosis and reactive oxygen species(ROS)were detected by flow cytometry,mitochondrial membrane potential was detected by JC-1,and mitochondrial fusion protein 1(Mfn1),mitochondrial fusion protein 2(Mfn2),dynamin related protein 1(Drp1),mitochondrial fission protein 1(FIS1),cytochrome c(CytC),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase(Caspase-3)expression were detected by Western blotting(WB).GraphPad Prism 8 statistics was used for data analysis,multiple groups comparisons were conducted using one-way analysis of variance,and LSD-t test was performed for pairwise multiple comparisons.Results H9c2 cardiomyocytes were used to establish OGD cell model,and the morphology of cardio-myocytes was signifcantly improved by S/V treatment under light microscope.Flow cytometry analysis showed that S/V significantly reduced the level of intracellular ROS and inhibited cardiomyocyte apoptosis(P＜0.05).Fluorescence microscope analysis showed that S/V significantly improved the level of mitochondrial membrane potential(P＜0.05);WB showed S/V significantly increase the protein expression levels of Mfn2,mfn1 and Bcl-2,and reduce the protein expression levels of Drp1,FIS1,CytcC,Bax and Caspase-3(P＜0.05).Conclusion S/V may regulate mitochondrial homeostasis,reduce ROS production and cardiomyocyte apoptosis by promoting mitochondrial fusion and inhibiting mitochondrial division.
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