Role of mitochondrial calcium uniporter in hypoxic preconditioning / 中国病理生理杂志

ABSTRACT

AIM: To investigate the role of mitochondrial calcium uniporter (MCU) in the cardioprotection by hypoxic preconditioning (HPC) and its relationship to mitochondrial permeability transition pore (MPTP). METHODS: Intraventricular balloon technique was employed to measure the left ventricular developed pressure (LVDP), the maximum rise/fall rate of left ventricular pressure (?dp/dt_ max ), and the left ventricular end-diastolic pressure (LVEDP) in Langendorff isolated rat heart. The hypoxia was achieved by ligation of left anterior coronary artery for 30 min followed by release of ligation for 120 min as reoxygenation. Hypoxic preconditioning was set as two episodes of 5 min global hypoxia and 5 min reoxygenation. RESULTS: Both HPC and treatment with ruthenium red (5 ?mol/L) during the first 10 min reoxygenation improved recovery of LVDP, ?dp/dt_ max and decreased LVEDP, which was associated with reduced infarct size and lactate dyhydrogenase release. These protective effects were attenuated by treatment with spermine (20 ?mol/L) during the first 10 min reoxygenation. Administration of cyclosporin A (0.2 ?mol/L) during the last 5 min of hypoxia period and first 15 min of reoxygenation period reduced the injury effect by spermine. CONCLUSION: These results indicate that inhibition of MCU is involved in the cardioprotection of HPC via inhibiting MPTP.