BACKGROUNDPrevious studies suggested that mechanical intervention during early reperfusion, or ischemia postconditioning (IPo), could protect kidneys against renal ischemia reperfusion injury (RIRI). However, the mechanisms responsible for this protection remain unclear. This study therefore investigated the protection afforded by IPo in rat kidneys in vivo, and the roles of mitochondrial K(ATP) channels (mitoK(ATP)) and mitochondrial permeability transition pores (MPTPs), by inhibiting mitoK(ATP) with 5-hydroxydecanoate (5-HD), and by directly detecting open MPTPs using calcein-AM and CoCl₂.

METHODSThirty-five male Sprague-Dawley rats were randomly assigned to sham-operation (S), ischemia-reperfusion (I/R), IPo, ischemia reperfusion with 5-HD (I/R + 5-HD), or IPo with 5-HD (IPo + 5-HD) groups. Rats in each group were sacrificed after 6 hours of reperfusion by heart exsanguination or cervical dislocation under anesthesia. RIRI was assessed by determination of creatinine and blood urea nitrogen (BUN), and by examination of histologic sections. The roles of mitoK(ATP) and MPTP were investigated by analyzing fluorescence intensities of mitochondria, mitochondrial membrane potential, intracellular reactive oxygen species (ROS) and intracellular calcium, using appropriate fluorescent markers. The relationship between apoptosis and RIRI was assessed by determining the apoptotic index (AI) of kidney tubular epithelial cells.

RESULTSThe RIRI model was shown to be successful. Significantly higher levels of creatinine and BUN, and abnormal pathology of histologic sections, were observed in group I/R, compared with group S. 5-HD eliminated the renoprotective effects of IPo. Mitochondrial and mitochondrial membrane potential fluorescence intensities increased, and intracellular calcium, ROS fluorescence intensities and AI decreased in group IPo, compared with group I/R. However, mitochondrial and mitochondrial membrane potential fluorescence intensities decreased, and intracellular calcium and ROS fluorescence intensities and AI increased in group IPo + 5-HD, compared with group IPo.

CONCLUSIONSmitoK(ATP) and MPTPs participated in IPo-induced renoprotective mechanisms in rat kidneys subjected to RIRI, possibly through decreased renal tubular epithelial cell apoptosis.