Previous studies from our group have demonstrated that
sevoflurane post-conditioning (SPC) protects against
myocardial ischemia reperfusion injury via elevating the intranuclear expression of
hypoxia inducible factor-1 alpha (HIF-1α). However, diabetic SPC is associated with decreased myocardial protection and disruption of the HIF-1 signaling pathway. Previous studies have demonstrated that
cobalt chloride (CoCl2) can upregulate HIF-1α expression under diabetic conditions, but whether myocardial protection by SPC can be restored afterward remains unclear. We established a rat model of
type 2 diabetes and a Langendorff isolated heart model of
ischemia-reperfusion injury. Prior to reperfusion, 2.4%
sevoflurane was used as a post-conditioning treatment. The diabetic rats were treated with CoCl2 24 h before the experiment. At the end of reperfusion, tests were performed to assess myocardial function,
infarct size, mitochondrial morphology,
nitric oxide (NO), Mitochondrial
reactive oxygen species (ROS), mitochondrial respiratory function and
enzyme activity, HIF-1α,
vascular endothelial growth factor (
VEGF) and endothelial
NO synthase (eNOS)
protein levels. In addition, myocardial protection by SPC was monitored after the
blood glucose levels were lowered by
insulin. The diabetic state was associated with deficient SPC protection and decreased HIF-1α expression. After treating the diabetic rats with CoCl2, SPC significantly upregulated the expression of HIF-1α,
VEGF and eNOS, which markedly improved cardiac function, NO, mitochondrial respiratory function, and
enzyme activity and decreased the
infarction areas and ROS. In addition, these effects were not influenced by
blood glucose levels. This study proved that CoCl2activates the HIF-1α signaling pathway, which restores SPC-dependent myocardial protection under diabetic conditions, and the protective effects of SPC were independent of
blood glucose levels.