Calcineurin mediates the protective effect of postconditioning on skeletal muscle.

ABSTRACT We aimed to investigate whether ischemic postconditioning (I-postC) protects skeletal muscle against ischemia-reperfusion (I/R) injury through the calcineurin (CaN) pathway. Male Wistar rats underwent 4 h of right-hind-limb ischemia induced by clamping the femoral artery, then reperfusion for 2 h (I/R-2 h), 12 h (I/R-12 h), or 24 h (I/R-24 h) with or without I-postC. Ischemic postconditioning was induced by three cycles of 1-min reperfusion and 1-min ischemia at the onset of reperfusion after prolonged ischemia. The I-postC-24 h group was treated with or without cyclosporine A (a CaN inhibitor) 10 mg/kg per day for 3 days before artery occlusion. Cultured skeletal muscle cells (SMCs) from neonatal rats were exposed to 2-h hypoxia then 24-h reoxygenation (H/R), then postconditioned with two cycles of 10-min reoxygenation and 10-min hypoxia after prolonged hypoxia (hypoxia postconditioning [H-postC]) in the presence or absence of cyclosporine A. We observed the effects of activated CaN overexpression on apoptosis and viability of SMCs under H-postC. Ischemic postconditioning attenuated the increase in the level of malondialdehyde in skeletal muscle induced by I/R-2 h and I/R-24 h (P