Dexmedetomidine (25 μg/kg, i.p., based on the previous organ protection studies [19 (link),27 (link)]) was administered 30 minutes before or immediately after renal ischemia-reperfusion injury (rIRI). One cohort was treated with the α2 adrenoceptor antagonist atipamezole (250 μg/kg, i.p. [19 (link),27 (link)]) prior to the administration of dexmedetomidine. The naive group and the rIRI group served as negative and positive controls, respectively. The animals were sacrificed 24 hr after rIRI. Kidneys were harvested for H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. All assessments were made by an investigator who was blinded to the experimental protocols. rIRI was induced either by bilateral renal pedicle clamping for 25 minutes to produce moderate renal injury, or by right renal pedicle clamping for 40 minutes and left nephrectomy to produce life-threatening renal injury, under 1.5% isoflurane surgical anesthesia. Sham-operated mice had dissection as above, but with no occlusion of the renal vessel. The intra-abdominal temperature was maintained at 36 ± 0.1°C with a heating pad which was servo-adjusted by a temperature controller (Engineering Inc, Stamford, CT, USA) throughout the experiment. For survival experiments, mice were monitored on a daily basis with a scoring assay based on body weight, activity and general appearance as reported previously. Any animals that scored > 7 were euthanized. All animals received 0.5 ml saline i.p. injection per every 6 hrs for the first 24 hrs after experiments.
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