Protective Effect of Sodium Hydrosulfide on Lipopolysaccharide Induced Myocardial Cell Injury Model: Involvement of Oxidative Stress and Endoplasmic Reticulum Stress

Abstract

Lipopolysaccharide can induce myocardial cell injury, which has been widely used in the preparation of septic cardiomyopathy models. We herein aimed to evaluate the protective effects of sodium hydrosulfide against oxidative stress and endoplasmic reticulum stress on the cell model of septic cardiomyopathy and to explore whether the protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic initiation factor 2 alpha signaling pathways was involved. The sepsis induced cardiomyopathy model which was established by inducing rat cardiomyoblast cell line H9c2 cells with lipopolysaccharide and sodium hydrosulfide and endogenous hydrogen sulfide inhibitor (DL-propargylglycine) were used for intervention treatment. Then, cell viability, endogenous hydrogen sulfide levels, lactate dehydrogenase, reactive oxygen species, superoxide dismutase, glutathione and malondialdehyde were determined using commercial assay kits; enzyme-linked immunosorbent assay was used to determine creatine kinase-myoglobin binding, interleukin-6, tumor necrosis factor alpha and interleukin-10; reverse transcription-polymerase chain reaction was used to determine cystathionine gamma-lyase messenger RNA expression; and Western blot was used to determine glucose-regulated protein 78, protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase, eukaryotic initiation factor alpha, phosphorylated eukaryotic initiation factor alpha, activating transcription factor 4 and C/EBP-homologous protein levels. Sodium hydrosulfide increased the hydrogen sulfide contents of cells, but did not affect the messenger RNA expression of cystathionine gamma-lyase. It attenuated the decrease in cell viability caused by lipopolysaccharide; reduced the release of the myocardial enzymes like lactate dehydrogenase and creatine kinase-myoglobin binding; reduced the level of inflammatory factors like interleukin-6 and tumor necrosis factor alpha; reduced the level of oxidative stress; inhibited the expression of protein kinase RNA-like endoplasmic reticulum kinase pathway proteins. Sodium hydrosulfide treatment improves septic cardiomyopathy by inhibiting oxidative stress and endoplasmic reticulum stress via the protein kinase RNA-like endoplasmic reticulum kinaseeukaryotic initiation factor alpha pathway, which may be a theory for the treatment of septic cardiomyopathy.