Effect of dexmedetomidine on expression of antisense hypoxia-inducible factor-1α during brain injury after asphyxial cardiac arrest and resuscitation in rats

Abstract

Objective To evaluate the effect of dexmedetomidine on the expression of antisense hypoxia-inducible factor-1α (aHIF-1α) during brain injury after asphyxial cardiac arrest and resuscitation in rats. Methods Twenty-four pathogen-free healthy male Sprague-Dawley rats, weighing 250-280 g, were divided into 3 groups (n=8 each) using a random number table: sham operation group (group S), cardiac arrest and resuscitation group (group R) and dexmedetomidine group (group D). Asphyxial cardiac arrest and resuscitation were performed in R and D groups.The rats were tracheally intubated without clipping the trachea in group S. Dexmedetomidine 4 μg/kg was injected via the tail vein at 5 min before clipping the trachea in group D, while the equal volume of normal saline was given instead in S and R groups.Neurological deficit was assessed and scored (NDS) at 12, 24, 48 and 72 h after recovery of spontaneous circulation (T1-4). The rats were sacrificed after assessing neurological deficit at T4, brains were removed and hippocampi were isolated for determination of cell apoptosis (by TUNEL), HIF-1α expression (by Western blot) and expression of HIF-1α and aHIF-1α mRNA in hippocampal tissues (using polymerase chain reaction). Apoptosis rate was calculated. Results Compared with group S, the NDS at each time point and apoptosis rate of hippocampal neurons at T4 were significantly increased, and the expression of HIF-1α protein and mRNA and 5′aHIF-1α mRNA was up-regulated in R and D groups (P<0.05). Compared with group R, the NDS at T2-4 and apoptosis rate of hippocampal neurons at T4 were significantly decreased, the expression of 5′aHIF-1α mRNA was down-regulated, and the expression of HIF-1α protein and mRNA was up-regulated in group D (P<0.05). Conclusion The mechanism by which dexmedetomidine reduces brain injury after asphyxial cardiac arrest and resuscitation is related to down-regulation of 5′aHIF-1α expression in rats. Key words: Dexmedetomidine; Hypoxia-inducible factor 1, alpha subunit; RNA, antisense; Hypoxia-ischemia, brain