The Regulation Mechanism Of HIF-1 Alpha On MPTP Channel In High Glucose H9c2 After Sevoflurane Postconditioning

Objectives: To investigate the regulation mechanism of Hypoxia-inducible factor1-alpha(HIF-1α) on Mitochondrial Permeability Transition Pore in high glucose condition, and to reveal the key molecular targets of myocardial ischemia reperfusion injury in high glucose. Methods: Establishment of a model of hypoxia and re-oxygenation injury by using H9c2, The levels of lactate dehydrogenase(LDH) and CCK-8 were detected by kit Cell apoptosis was detected by TUNELmethod; The changes of Mitochondrial Permeability Transition Pore and mitochondrial membrane potential were detected by laser confocal microscopy; The expression of HIF-1αand HexokinaseII(HKII) was detected by Western blot method; The content and distribution of HKII were detected by immunofluorescence assay. Results: 1) Compared with the normal group,hypoxia and reoxygenation oxygen damage and Sevoflurane Postconditioning can be upregulation of HIF-1 alpha protein expression, which upregulation of sevoflurane is more significant, HIF-1 alpha can inhibition of mPTP opening and reduce cell apoptosis;2) The expression of HKII in the downstream target gene of HIF-1 alpha was significantly inhibited and the open of mPTP increased, so that the cell damage was obvious; 3) inhibition of HKII after HIF-1 alpha loss to the mPTP regulation, Sevoflurane Postconditioning lost its myocardial protective effect; 4) in high glucose conditions, using Sevoflurane Postconditioning did not reduce the myocardial cell apoptosis. The expression of HIF-1 alpha and HKII than normal Sevoflurane Postconditioning group had no significant difference, but the existence of HKII to the cell membrane aggregation phenomenon. Conclusion: In hypoxia reoxygenation injury after Sevoflurane Postconditioning can upregulate the expression of HIF-1 alpha protein producemyocardial protection. The mechanism may be up regulation of HIF-1 alpha to activate its downstream target gene HKII, Inhibiting the opening of mPTP, which can reduce the damage of myocardial cells caused by hypoxia and re-oxygenation. Under high glucose condition, the protective effect of sevoflurane decreased or disappeared due to HKII translocation leads to HIF-1 alpha lose the control function of mPTP, Therefore, the necrosis and apoptosis of myocardial cells induced by hypoxia and re-oxygenation under high glucose were increased.