Effects Of Intermittent Hypoxia On Oxidative Stress Injury Of Myocardial In Rats And The Intervention Effect Of Edaravone

Objective To study the effects of intermittent hypoxia on oxidative stress injury of myocardial in rats and the intervention effect of edaravone,and to explore the mechanism of oxidative stress injury.Methods To establish a intermittent hypoxia(IH)animal model in rats,in order to mimic the intermittent hypoxia of obstructive sleep apnea hypopnea syndrome(OSAHS)in humans.To study effect of intermittent hypoxia on oxidative stress injury of myocardial in rats and the intervention effect of edaravone.According to the random numble table,a total of 80 healthy male wistar rats were divided into four experimental groups: normoxic control group(NC group),conventional intermittent hypoxia group(CIH group),intermittent hypoxia edaravone treatment group(CIH +Eda group),intermittent hypoxia normal saline matched group(CIH + NS group),with 20 rats in each group.Firstly,the IH group,IH+Eda group and IH+NS group were respectively placed in an animal chamber subjected to intermittent hypoxic(nadir ambient oxygen concentration 6-7%,maximum ambient oxygen concentration20-21%),NC group was subjected to compressed air for eight hours per day and the experimental lasted for 28 days.Second,the IH+Eda group was established through intraperitoneal injection of edaravone,IH+NS group was established by injecting of nomal saline.After the experiment,we mensured the level of serum LDH,CK,CK-MB and myocardial tissue MDA,SOD and hydroxyl radical.The changes of myocardial histopathology and ultrastructure of myocardial cells were observed by light microscope and transmission electron microscope.Determination of ATP in myocardial cells was confirmed the impaired mitochondrial function.The expression of bcl-2,Bax and Caspase3 m RNA was determined by reverse transcription-polymerase chain reaction(RT-PCR)to clear myocardial apoptosis.Results Firstly,compared with NC group,serum myocardial enzyme LDH,CK,CK-MB,myocardial tissue MDA,hydroxyl radical and myocardial cell Bax,Caspase3 mRNA were significantly increased in IH group.The myocardial tissue SOD,myocardial cell ATP and bcl-2 mRNA were significantly decreased.Secondly,myocardial tissue was damaged in light microscope and transmission electron microscope.Thirdly,to compared with IH+NS group,the expression of serum myocardial enzyme LDH,CK,CK-MB,myocardial tissue MDA and hydroxyl radicals and myocardial cell Bax,Caspase3 mRNA were significantly reduced in IH+Eda group.The myocardial tissue SOD,myocardial cell ATP and bcl-2 mRNA were significantly increased.In light microscope and transmission electron,the myocardial tissue were both relieved.Fourthly,the expression level of Caspase3 mRNA in myocardial cell was positively correlated with CK(r=0.575),CK-MB(r=0.460),MDA(r=0.643),hydroxyl radicals(r=0.454)and Bax mRNA(r=0.741),while negatively correlated with ATP(r=-0.525),Bcl-2mRNA(r=-0.578).Conclusions IH can upregulate the level of serum myocardial enzyme LDH,CK,CK-MB,myocardial tissue MDA,hydroxyl radical and myocardial cell Bax,Caspase3 mRNA.On the contrary,the myocardial tissue SOD,myocardial cell ATP and bcl-2 mRNA were significantly decreased.What’s more,myocardial tissue was damaged in light microscope and transmission electron microscope.Correlation analysis showed that the expression level of Caspase3 m RNA in myocardial cell was positively correlated with the contents of serum myocardial enzyme,myocardial tissue oxides,apoptosis gene,while negatively correlated with the contents of ATP and antiapoptotic gene.Intermittent hypoxia can caused oxidative stress of myocardium in rat by mitochondrial mediated apoptosis.Edaravone can prevent this damage,which protect the cardiomyocytes in rats.