Effects of selective brain hypothermia on expression of miR-484 during cerebral ischemia-reperfusion in rats

Abstract

Objective \nTo evaluate the effects of selective brain hypothermia on the expression of miR-484 during cerebral ischemia-reperfusion (I/R) in rats. \n \n \nMethods \nA total of 120 clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups (n=30 each) using a random number table method: sham operation group (group S), cerebral I/R group (group I/R), hypothermia group (group H) and normothermia group (group N). Blood vessels were only separated and ligated without blockade in group S. In the other three groups, cerebral I/R was induced by inserting a nylon thread with rounded tip into the right internal carotid artery, and the middle cerebral artery was occluded for 2 h followed by reperfusion.In group H, 4 ℃ normal saline was infused for 15 min at a rate of 80 ml·kg-1·h-1 through the internal carotid artery immediately after removing the nylon thread.In group N, 37 ℃ normal saline was infused in the same way.Neurological deficit scores were evaluated at 6, 24 and 48 h after reperfusion.Animals were then sacrificed, the cerebral cortex of the ischemic penumbra was removed for determination of nerve cell apoptosis (by TUNEL method), expression of mitochondrial fission protein 1 (Fis1) (by Western blot) and expression of miR-484 (quantitative real-time polymerase chain reaction). The apoptotic rate was calculated. \n \n \nResults \nCompared with group S, the neurological deficit score and apoptotic rate of nerve cells were significantly increased, and the expression of Fis1 was up-regulated at each time point in the other three groups, the expression of miR-484 was significantly down-regulated in I/R and N groups, and the expression of miR-484 was significantly up-regulated in group H (P<0.05 or 0.01). Compared with group I/R and group N, the neurological deficit score and apoptotic rate of nerve cells were significantly decreased, and the expression of Fis1 was down-regulated, and the expression of miR-484 was up-regulated at each time point in group H (P<0.05 or 0.01). \n \n \nConclusion \nThe mechanism by which selective cerebral hypothermia attenuates cerebral I/R injury is associated with up-regulating miR-484 expression and thus down-regulating Fis1 expression in rats. \n \n \nKey words: \nHypothermia;\xa0Brain;\xa0Reperfusion injury;\xa0MicroRNAs