| Objective:to explore the effect of intermittent hypoxia on myocardial injury in rats,and to analyze the correlation between intermittent hypoxia and HMGB1/RAGE,TLR4/TNF-α signal pathway and the intervention effect of daravone,so as to find a new treatment for OSAHS complicated with myocardial injury.Methods:eighteen four-week-old healthy male Sprague-Dawley(SD)rats were randomly divided into three groups:normal control group(NC),intermittent hypoxia group(CIH)and intermittent hypoxia+Edaravone treatment group(CIH+EDA).After the establishment of the model,the blood samples of rats in each group were taken to determine the levels of lactate dehydrogenase(LDH),creatine kinase(CK)and creatine kinase isoenzyme(CK-MB).The histological changes of myocardial specimens in each group were observed by hematoxylin-eosin staining(HE),and the degree of myocardial fibrosis was observed by Masson staining.The expressions of high mobility histone B1(HMGB1),advanced glycation end products receptor(RAGE),Toll-like receptor 4(TLR4)and tumor necrosis factor-α(TNF-α)in myocardial tissue of rats in each group were observed by immunohistochemistry and Western blotting.Results:(1)The results of serum myocardial enzymes in each group showed that the levels of LDH and CK-MB in CIH group were higher than those in NC group,but the level of CK was not significantly higher than that in CIH group.The levels of LDH,CK and CK-MB in CIH+EDA group were lower than those in CIH group.(2)The effect of intermittent hypoxia on the morphology of cardiomyocytes and the intervention effect of Edaravone:compared with NC group,the arrangement of cardiomyocytes in CIH group was disordered,loose,cardiomyocytes were broken,and the myocardial space was significantly widened,including inflammatory cell infiltration and increased degree of fibrosis.After the intervention of Edaravone,it was observed that the arrangement of cardiomyocytes was neat,the myocardial space changed slightly,and the degree of fibrosis was alleviated.(3)The effect of intermittent hypoxia on the expression of proteins in HMGB1/RAGE and TLR4/TNF-α pathway and the intervention effect of Edaravone:compared with NC group,the expression levels of HMGB1,RAGE,TLR4 and TNF-αin CIH group were higher than those in CIH group.The expression levels of HMGB1,RAGE,TLR4 and TNF-α in CIH+EDA group were lower than those in CIH group.Conclusion:(1)The main results are as follows:intermittent hypoxia can induce the increase of myocardial enzyme level in SD rats and cause myocardial injury to a certain extent.(2)intermittent hypoxia stimulation can cause cardiomyocyte arrangement disorder,breakage and fibrosis.(3)HMGB1/RAGE and TLR4/TNF-α signal pathways may be involved in intermittent hypoxia-induced myocardial injury in rats.(4)Edaravone can reduce the inflammatory response by down-regulating the expression of proteins in HMGB1/RAGE and TLR4/TNF-α signal pathway,thus alleviating myocardial injury to a certain extent. |
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