title: Protective role of mitochondrial K-ATP channel and mitochondrial membrane transport pore in rat kidney ischemic postconditioning.
abstract: BACKGROUND
  Previous 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.
  
  
  METHODS
  Thirty-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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  mitoK(ATP) and MPTPs participated in IPo-induced renoprotective mechanisms in rat kidneys subjected to RIRI, possibly through decreased renal tubular epithelial cell apoptosis.
authors.affiliation: Department of Anesthesiology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Zhang
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Zhao
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D057775:Ischemic Postconditioning; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; D002118:Calcium