Changes of myocardial oxidative stress injury and intervention of edaravone in intermittent hypoxic rat model

Abstract

Objective To investigate the effect of intermittent hypoxia (IH) on myocardial oxidative stress injury and its possible mechanism by establishing IH rat model, and to further understand the intervention effect of edaravone, provide new ideas for the research and prevention of obstructive sleep apnea-hypopnea syndrome and related cardiovascular complications. Methods Eighty healthy male Wistar rats were randomly divided into normal control (NC) group, IH group, IH+ edaravone group, and IH+ normal saline (NS) group, 20 rats in each group.The IH rat model was established by using a gas control device to fill the closed simulation chamber with nitrogen, oxygen and compressed air.After four weeks of modeling, the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CK-MB) and malondialdehyde (MDA), superoxide dismutase (SOD) and hydroxyl radicals were measured.The mitochondrial adenosine triphosphate (ATP) level in cardiomyocytes was measured.Myocardial morphology and ultrastructure were observed by light microscopy and transmission electron microscopy.Transcription-polymerase chain reaction technique was used to detect the expressions of Bcl-2, Bax and Caspase-3 mRNA in myocardial tissue. Results (1)Compared with the NC group, the levels of LDH, CK, CK-MB, MDA and hydroxyl radicals, the expressions of Bax and Caspase-3 mRNA were significantly increased, while the SOD activity, ATP content, and the expression of Bcl-2 mRNA were significantly decreased in the IH group and the IH+ NS group (all P<0.05). (2)Under light microscope and transmission electron microscope, no obvious damage was found in myocardial tissue of NC group, but the morphology and ultrastructure of myocardial tissue in IH group and IH+ NS group were damaged.(3)After intervention with edaravone, serum LDH, CK, CK-MB and myocardial tissue MDA, hydroxyl radicals, Bax and Caspase-3 mRNA expressions decreased, SOD activity and ATP content increased, Bcl-2 mRNA expression level was elevated (all P<0.05), and the degree of myocardial tissue damage under light and electron microscopy was alleviated.(4)Caspase-3 mRNA expression in cardiomyocytes was positively related with CK (r=0.575), CK-MB (r=0.460), MDA (r=0.643), hydroxyl radical (r=0.454), and Bax mRNA (r=0.741), negatively related with ATP (r=-0.525) and Bcl-2 mRNA (r=-0.578). Conclusions (1)IH can induce myocardial oxidative stress damage in rats by increasing oxidants, reducing antioxidants and activating Bcl-2, Bax and Caspase-3.(2)The myocardial oxidation stress injury induced by IH may be achieved by mitochondria-mediated apoptosis.(3)Edaravone has an intervention effect on myocardial injury induced by IH. Key words: Intermittent hypoxia; Oxidative stress; Myocardial injury; Adenosine triphosphate; Edaravone; Apoptosis