The Beneficial Effects Of Chronic Intermittent Hypobaric Hypoxia On Dilatation Cardiomyopathy

Chronic intermittent hypobaric hypoxia?CIHH?treatment can improve the hypoxic tolerance of various tissues.The activation of hypoxia inducible factor-1?HIF-1?participates in the protective effects of CIHH on hypoxia injury.CIHH treatment can activate HIF-1,which mediates its downstream hypoxia response protein expression,such as vascular endothelial growth factor?VEGF?,nitric oxide synthase,erythropoietin and so on.Dilated cardiomyopathy?DCM?is a primary myocardial disease characterized by ventricular systolic and diastolic dysfunction.Myocardial microcirculation dysfunction may be one of the pathogenesis of DCM.The VEGF induced by CIHH treatment can promote the regeneration of myocardial capillary and improve local microcirculation.This may provide new ideas for the clinical treatment of DCM.In this study,the cTnT^R141Wtransgenic DCM mice was treated with CIHH and the following studies were performed.In the first part,we detected the cardiac structure and function parameters of mice by using ultrasound to clarify the effects of CIHH treament on DCM.In the second Part,we investigated the role of HIF1-VEGF pathway by using molecular biology methods.Part one The effects of CIHH on the cardiac structure and function of DCMObjective:To investigate the effects of CIHH on the cardiac structure and function in DCM miceMethods:Twenty 8-week-old male cTnT^R141Wtransgenic DCM mice and 20 wild-type C57 mice were randomly divided into 4 groups:Control group,Control+CIHH group,DCM group,and DCM+CIHH group.Control+CIHH and DCM+CIHH mice received CIHH treatment.The mice in the Control group and the DCM group were kept in normoxic environment.Small animal ultrasound was used to measured the cardiac structural and functional parameters.Results:Compared with the Control group,the ratio of heart weight to body weight in the DCM group was increased?P<0.05?.Compared with the DCM group,the ratio of heart weight to body weight in the DCM+CIHH group was significantly higher at the 4th week after CIHH treatment.Decrease?P<0.05?.Compared with the Control group,the left ventricular end-systolic diameter and left ventricular end-diastolic diameter in the DCM group were significantly increased?P<0.05?,left ventricular end-systolic volume and left ventricular end diastolic volume were significantly increased?P<0.05?.Ventricular septal motion velocity and left ventricular wall motion velocity were significantly reduced?P<0.05?,ejection fraction and left ventricular short axis shortened rate were significantly reduced?P<0.05?;compared with DCM group,given CIHH treatment second At week 4 and week 4,the left ventricular end-systolic diameter and left ventricular end-diastolic diameter in DCM+CIHH mice were shortened?P<0.05?,left ventricular end-systolic volume and left ventricular end diastolic volume were significantly decreased?P<0.05?.The velocity of interventricular septum movement and posterior left ventricular wall velocity?P<0.05?,ejection fraction,and left ventricular short axis shortened significantly?P<0.05?.Conclusion:CIHHcanincreasethemovementvelocityof interventricular septum and left ventricular posterior wall,decrease the left ventricular end-diastolic diameter,left ventricular end-systolic diameterand,left ventricular end-systolic,left ventricular end-diastolic volume,improve the ejection fraction and short left ventricular shortening rate in DCM mice.These effects suggest that CIHH treatment shows beneficial effects on DCM.Part two:The role of HIF1-VEGF pathway in the cardiac protection effects of CIHH on DCM.Objective:To explore the possiblemechanism of CIHH-induced cardiac protection effects on DCM by studying the expression level of HIF1-VEGF pathway.Methods:The serum VEGF level was determined by ELISA.The expression of HIF-1?and VEGF protein in myocardial tissue was detected by Western Blot.The expression of HIF-1?mRNA and VEGF mRNA were detected by RT-PCR.Results:Compared with the Control group,the serum VEGF levels in the DCM group,Control+CIHH group,and DCM+CIHH group were significantly higher than those in the Control group?P<0.05?.The expression of HIF-1?and VEGF in myocardial tissue of mice in the DCM group was significantly increased.The levels of HIF-1?mRNA and VEGFmRNA in myocardium of mice in DCM group were significantly increased?P<0.05?.Compared with DCM group,the serum levels of VEGF in mice of DCM+CIHH group increased?P<0.05?.0.05),the expression of HIF-1?and VEGF in myocardial tissue was increased?P<0.05?,and the expression of HIF-1?mRNA and VEGFmRNA in myocardial tissue was up-regulated?P<0.05?.Conclusion:CIHH treatment can increase serum VEGF in DCM mice and upregulate mRNA and protein expression of HIF-1?and VEGF in myocardial tissue,suggesting that myocardial microvascular regeneration may be one of the molecular mechanisms of the cardiac protection effects of CIHH on DCM.