关键词: 环孢素A (CsA), 七氟醚后处理 (SPostC), 高糖, 原代心肌细胞, 缺氧/复氧损伤

Abstract: Objective To evaluate whether cyclosporin A (CsA) restore the cardioprotective effect of sevoflurane postconditioning (SPostC) against hypoxia /reoxygenation (H/R) injury in rat under high concentration of glucose through inhibiting mitochondrial permeability transition pore opening and maintaining mitochondrial morphology. Methods Primary cultures of neonatal rat cardiomyocytes in low and high concentrations of glucose for 48 h were subjected to HR (3 hr hypoxia followed by 3 hr reoxygenation), treated with SPostC before perfusion or CsA before gypoxia, or combined use of these two interventions were performed before hypoxia. Cell death, lactate dehydrogenase (LDH) level, mitochondrial morphology and mitochondrial membrane potential were measured after H/R injury. Results Both SPostC and CsA decreased cell death, LDH level, increased mitochondrial interconnectivity and mitochondrial membrane potential following H/R (P<0.05), combination of these two interventions did not further enhance the protective effects. High concentration of glucose (35 mmol/L) eliminated the cardioprotective effect mentioned above. As compared with high glucose group, SPostC or CsA, or combined use of these two interventions did not affect the cell death, LDH level, mitochondrial interconnectivity and mitochondrial membrane potential following H/R (P<0.05). Conclusion Both SPostC and CsA can protect cardiomyocytes against H/R injury through maintaining mitochondrial morphology. High concentration of glucose eliminates the cardioprotective effect, and CsA can not restore the cardioprotective effect of SPostC under high concentration of glucose.

Key words: Cyclosporin A (CsA), Sevoflurane postcondition (SPostC), High glucose, Hypoxia/reoxygenation (H/R) injury, Primary neonatal rat cardiomyocytes