Nocturnal hypoxemia during sleeping hours or intermittent hypoxia implicated in the pathogenesis of cardiac complications was often reported in severe obesity. The main purpose of this study was to explore the cardiac apoptosis in obese Zucker Rat under long-term intermittent hypoxia. Twelve obese Zucker rats and twelve age-matched lean Zucker rats were divided into four groups including normoxia in lean group, normoxia in obese group，hypoxia in lean group, and hypoxia in obese group. The hypoxia group were housed in a hypoxic chamber (12% O2, 88% N2), 8 hour per day for 7 days. The key components of mitochondrial-dependent apoptotic pathway, Fas recetopr-dependent apoptotic pathway and apoptotic cardiomyocytes in the excised left ventricle from rats were measured by Western blotting, reverse transcription polymerase chain reaction (RT-PCR) and Tunnel assay. The activity levels of death-receptor pathway (Fas、FADD、Bid、activated-Caspase 8 and activated-Caspase 3) and mitochondrial dependent apoptotic pathway (BNIP3, Bad and cytosolic cytochrome c, activated caspase 9) were increased in lean rat heart after long-term intermittent hypoxia. The activity levels of death-receptor pathway and mitochondrial dependent apoptotic pathway were increased in obese rat hearts, compared with lean rat heart and further increased after long-term intermittent hypoxia in obese rat hearts, compared with either lean in hypoxia group or obese in normoxia group. Long term intermittent hypoxia and obesity itself would make additively deleterious effects on cardiac tissues in obese Zucker Rat. Our findings imply that intermittent hypoxia and obesity itself will additively increases cardiac apoptosis in obese rat heart through mitochondrial dependent apoptotic pathway and death receptor dependent pathway.
