PGC-1? Participates In The Protective Effect Of Chronic Intermittent Hypobaric Hypoxia On Cardiomyocytes

Chronic intermittent hypobaric hypoxia?CIHH?has obvious cardioprotective effects.Cardiomyocytes energy metabolism plays an important role in normal cardiac functions.To further understand whether the improvement of cardiomyocytes metabolism participated in the cardioprotective effect of CIHH remains unclear,in this study,we determined whether and how peroxisome proliferator-activated receptor gamma coactivator1-alpha?PGC-1??and its related pathway involved in cardiomyocytes of CIHH.Method:Adult male Sprague-Dawley rats were randomly divided into two groups:control group?CON?and chronic intermittent hypobaric hypoxia group?CIHH?.CIHH rats received a hypobaric hypoxia simulating 5000m altitude for 28 days,6 hours each day,in hypobaric chamber.Rat ventricular myocytes were obtained by enzymatic dissociation and the intracellular calcium concentration([Ca²⁺]_i)were measured using laser scanning confocal microscopy after hypoxia/reoxygenation treatment?H/R?.PGC-1?siRNA adenovirus transfection was used to knock down PGC-1?gene expression of cardiomyocytes.The mRNA and protein expressions involved in cardiac energy metabolism were determined using realtime PCR and Western blot techniques.Results:CIHH treatment decreased[Ca²⁺]_i elevation?P<0.01?and cTnI protein expression increase?P<0.01?in cardiomyocytes after H/R.Both mRNA and protein expression of PGC-1?increased after CIHH treatment,which was dramatically decreased by PGC-1?siRNA adenovirus transfection.In addition,PGC-1?knocking down also abolished the increased protein expression of GLUT4 protein?P<0.01?,and decreased protein expression of CPT-1b?P<0.01?in cardiomyocytes by CIHH treatment.Furthermore,CIHH treatment increased the expression of HIF-1?,AMPK and p-AMPK in cardiomyocytes,and pretreatment with AMPK blockers dorsomorphin abolished the enhancement of PGC-1?protein expression in cardiomyocytes by CIHH treatment?P<0.01?.Conclusion:CIHH treatment could decrease the calcium overload caused by H/R injury in cardiomyocytes through up-regulating the expression of PGC-1?and regulating the energy metabolism of glucose and lipid.Activation of AMPK?HIF-1?might be involved in the process.